US20170191064A1 - Oligonucleotides for inducing paternal ube3a expression - Google Patents

Abstract

The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

Description

PRIORITY INFORMATION
• This application is a continuation and claims priority to PCT/EP2016/077383, filed Nov. 11, 2016, which claims priority to EP15194367.7, filed Nov. 12, 2015 and EP161895024, filed Sep. 19, 2016. The contents of which are hereby incorporated by reference.
FIELD OF INVENTION
• The present invention relates to oligonucleotides (oligomers) that are complementary to and hybridize to SNHG14 downstream of SNORD109B, leading to induction of paternal expression of Ubiquitin-protein ligase E3A (UBE3A) in an animal or human. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.
BACKGROUND
• Angelman syndrome is neuro-genetic disorder caused by deletion or inactivation of the UBE3A genes on the maternally inherited chromosome 15q11.2. The paternal copy of the UBE3A gene is subject to genomic imprinting and silencing in neurons by an endogenous antisense transcript of UBE3A, termed SNHG14 (also known as UBE3A-ATS) (Meng et al. 2012 Hum Mol Genet. Vol. 21 pp. 3001-12). Other cell types than neurons seem to express the UBE3A gene from both the maternal and paternal allele.
• Angelman syndrome is characterized by severe intellectual and developmental disability, sleep disturbance, seizures, jerky movements, EEG abnormalities, frequent laughter or smiling, and profound language impairments.
• WO 2012/064806 discloses a method of inducing UBE3A expression in a cell by using a topoisomerase inhibitor. The method can be used to treat Angelman syndrome. There is no disclosure of antisense oligonucleotides.
• WO 2014/004572 discloses oligonucleotides with 2′-O-methoxyethyl-RNA (MOE) modifications targeting mouse UBE3A-ATS. The oligonucleotides are only tested in mice related assays. In the region downstream of MBII-52 snoRNA (also known as SNORD115) and upstream of the UBE3A pre-mRNA there is no conservation between mouse and human. Oligonucleotides targeting mouse UBE3A-ATS can therefore not be translated into oligonucleotides that will function in a human. There is no disclosure of oligonucleotides targeting human UBE3A-ATS.
OBJECTIVE OF THE INVENTION
• The present invention identifies novel oligonucleotides which induce human paternal UBE3A expression in neuronal without affection expression of the paternal SNORD115, SNORD116 and SNRPN transcripts significantly.
SUMMARY OF INVENTION
• The present invention relates to oligonucleotides targeting a nucleic acid capable of suppressing the expression of UBE3A and to treat or prevent diseases related to decreased activity of UBE3A, in particular in neuronal cells.
• Accordingly, in a first aspect the invention provides oligonucleotides which comprise a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 98% complementarity to the part of human SNHG14 long non-coding RNA corresponding to position 25278410 to 25419462 on human chromosome 15 version GRCh38.p2. This region is also resembled by SEQ ID NO: 1. The oligonucleotide can be an antisense oligonucleotide, preferably with a gapmer design. Preferably, the oligonucleotide is capable of inducing the expression of UBE3A, in particular paternal UBE3A expression in a neuron, by degradation, reduction or removal of the UBE3A suppressor, in particular by reduction of the SNHG14 long non-coding RNA transcript downstream of SNORD109B. The UBE3A re-expression is achieved, without significantly affecting the expression of SNORD115. The degradation of the target nucleic acid is preferably achieved via nuclease recruitment.
• In a further aspect, the invention provides pharmaceutical compositions comprising the oligonucleotides of the invention and pharmaceutically acceptable diluents, carriers, salts and/or adjuvants.
• In a further aspect, the invention provides methods for in vivo or in vitro induction of UBE3A expression in a target cell where expression of paternal UBE3A is suppressed, by administering an oligonucleotide or composition of the invention in an effective amount to said cell.
• In a further aspect the invention provides methods for treating or preventing a disease, disorder or dysfunction associated with in vivo activity of UBE3A comprising administering a therapeutically or prophylactically effective amount of the oligonucleotide of the invention to a subject suffering from or susceptible to the disease, disorder or dysfunction.
• In a further aspect the oligonucleotide or composition of the invention is used for the treatment or prevention of Angelman syndrome.
BRIEF DESCRIPTION OF FIGURES
• FIG. 1: The upper strand illustrates the region of the SNHG14 transcript downstream of SNORD109B (UBE3A-ATS) where the black boxes indicate the location of the tested mouse oligonucleotides. The lower strand illustrates the UBE3A coding region, where the black boxes indicate exons. Exon 1 is located around 160 kb. The oligonucleotides are placed in the antisense region of Exon 9 (positioned at ˜97 kb), Exon 10 (positioned at ˜92 kb), Exon 13 (positioned at ˜77 kb) and the 5′ end of Exon 16 (positioned at ˜60 kb).
• FIG. 2: Representation of the ability of the oligonucleotides, tested in Example 2, to induce re-expression of UBE3A in human neuronal cell cultures. Oligonucleotides complementary to the region of human SNHG14 long non-coding RNA between SNORD109B and the region upstream of the UBE3A coding region (position 1 to 55318 of SEQ ID NO: 1) are indicated with  nonoverlap. Oligonucleotides complementary to the region of human SNHG14 long non-coding RNA which is antisense to the UBE3A pre-mRNA (position 55319 to 141053 of SEQ ID NO: 1) are indicated with ▴ overlap. Oligonucleotides from Table 3 with conservation to human and rhesus monkey are indicated at the bottom of each plot as

  

  . Conservation between human:rhesus:mouse is indicated by

  

  . The oligonucleotide concentrations were 0.2, 1 and 5 microM as indicated in the right hand side each plot.
DEFINITIONS Oligonucleotide
• The term “oligonucleotide” as used herein is defined as it is generally understood by the skilled person as a molecule comprising two or more covalently linked nucleosides. Such covalently bound nucleosides may also be referred to as nucleic acid molecules or oligomers. Oligonucleotides are commonly made in the laboratory by solid-phase chemical synthesis followed by purification. When referring to a sequence of the oligonucleotide, reference is made to the sequence or order of nucleobase moieties, or modifications thereof, of the covalently linked nucleotides or nucleosides. The oligonucleotide of the invention is man-made, and is chemically synthesized, and is typically purified or isolated. The oligonucleotide of the invention may comprise one or more modified nucleosides or nucleotides.
Antisense Oligonucleotides
• The term “Antisense oligonucleotide” as used herein is defined as oligonucleotides capable of modulating expression of a target gene by hybridizing to a target nucleic acid, in particular to a contiguous sequence on a target nucleic acid. The antisense oligonucleotides are not essentially double stranded and are therefore not siRNAs. Preferably, the antisense oligonucleotides of the present invention are single stranded.
Contiguous Nucleotide Sequence
• The term “contiguous nucleotide sequence” refers to the region of the oligonucleotide which is complementary to the target nucleic acid. The term is used interchangeably herein with the term “contiguous nucleobase sequence” and the term “oligonucleotide motif sequence”. In some embodiments all the nucleotides of the oligonucleotide are present in the contiguous nucleotide sequence. In some embodiments the oligonucleotide comprises the contiguous nucleotide sequence and may, optionally comprise further nucleotide(s), for example a nucleotide linker region which may be used to attach a functional group to the contiguous nucleotide sequence. The nucleotide linker region may or may not be complementary to the target nucleic acid.
Nucleotides
• Nucleotides are the building blocks of oligonucleotides and polynucleotides, and for the purposes of the present invention include both naturally occurring and non-naturally occurring nucleotides. In nature, nucleotides, such as DNA and RNA nucleotides comprise a ribose sugar moiety, a nucleobase moiety and one or more phosphate groups (which is absent in nucleosides). Nucleosides and nucleotides may also interchangeably be referred to as “units” or “monomers”.
Modified Nucleoside
• The term “modified nucleoside” or “nucleoside modification” as used herein refers to nucleosides modified as compared to the equivalent DNA or RNA nucleoside by the introduction of one or more modifications of the sugar moiety or the (nucleo)base moiety. In a preferred embodiment the modified nucleoside comprises a modified sugar moiety. The term modified nucleoside may also be used herein interchangeably with the term “nucleoside analogue” or modified “units” or modified “monomers”.
Modified Internucleoside Linkage
• The term “modified internucleoside linkage” is defined as generally understood by the skilled person as linkages other than phosphodiester (PO) linkages, that covalently couples two nucleosides together. Nucleotides with modified internucleoside linkage are also termed “modified nucleotides”. In some embodiments, the modified internucleoside linkage increases the nuclease resistance of the oligonucleotide compared to a phosphodiester linkage. For naturally occurring oligonucleotides, the internucleoside linkage includes phosphate groups creating a phosphodiester bond between adjacent nucleosides. Modified internucleoside linkages are particularly useful in stabilizing oligonucleotides for in vivo use, and may serve to protect against nuclease cleavage at regions of DNA or RNA nucleosides in the oligonucleotide of the invention, for example within the gap region of a gapmer oligonucleotide, as well as in regions of modified nucleosides.
• In an embodiment, the oligonucleotide comprises one or more internucleoside linkages modified from the natural phosphodiester to a linkage that is for example more resistant to nuclease attack. Nuclease resistance may be determined by incubating the oligonucleotide in blood serum or by using a nuclease resistance assay (e.g. snake venom phosphodiesterase (SVPD)), both are well known in the art. Internucleoside linkages which are capable of enhancing the nuclease resistance of an oligonucleotide are referred to as nuclease resistant internucleoside linkages. In preferred embodiments at least 50% of the internucleoside linkages in the oligonucleotide, or contiguous nucleotide sequence thereof, are modified, such as at least 60%, such as at least 70%, such as at least 80 or such as at least 90% of the internucleoside linkages in the oligonucleotide, or contiguous nucleotide sequence thereof, are modified. In some embodiments all of the internucleoside linkages of the oligonucleotide, or contiguous nucleotide sequence thereof, are modified. It will be recognized that, in some embodiments the nucleosides which link the oligonucleotide of the invention to a non-nucleotide functional group, such as a conjugate, may be phosphodiester. In some embodiments all of the internucleoside linkages of the oligonucleotide, or contiguous nucleotide sequence thereof, are nuclease resistant internucleoside linkages.
• Modified internucleoside linkages may be selected from the group comprising phosphorothioate, diphosphorothioate and boranophosphate. In preferred embodiments, the modified internucleoside linkages are compatible with the RNaseH recruitment of the oligonucleotide of the invention, for example phosphorothioate, diphosphorothioate or boranophosphate.
• In some embodiments the internucleoside linkage comprises sulphur (S), such as a phosphorothioate internucleoside linkage.
• A phosphorothioate internucleoside linkage is particularly useful due to nuclease resistance, beneficial pharmakokinetics and ease of manufacture. In preferred embodiments at least 50% of the internucleoside linkages in the oligonucleotide, or contiguous nucleotide sequence thereof, are phosphorothioate, such as at least 60%, such as at least 70%, such as at least 80 or such as at least 90% of the internucleoside linkages in the oligonucleotide, or contiguous nucleotide sequence thereof, are phosphorothioate. In some embodiments all of the internucleoside linkages of the oligonucleotide, or contiguous nucleotide sequence thereof, are phosphorothioate.
• In some embodiments, the oligonucleotide comprises one or more neutral internucleoside linkage, particularly a internucleoside linkage selected from phosphotriester, methylphosphonate, MMI, amide-3, formacetal or thioformacetal.
• Further internucleoside linkages are disclosed in WO2009/124238 (incorporated herein by reference). In an embodiment the internucleoside linkage is selected from linkers disclosed in WO2007/031091 (incorporated herein by reference). Particularly, the internucleoside linkage may be selected from —O—P(O)₂—O—, —O—P(O,S)—O—, —O—P(S)₂—O—, —S—P(O)₂—O—, —S—P(O,S)—O—, —S—P(S)₂—O—, —O—P(O)₂—S—, —O—P(O,S)—S—, —S—P(O)₂—S—, —O—PO(R^H)—O—, 0-PO(OCH₃)-0-, —O—PO(NR^H)—O—, —O—PO(OCH₂CH₂S—R)—O—, —O—PO(BH₃)—O—, —O—PO(NHR^H)—O—, —O—P(O)₂—NR^H—, —NR^H—P(O)₂—O—, —NR^H—CO—O—, —NR^H—CO—NR^H—, and/or the internucleoside linker may be selected form the group consisting of: —O—CO—O—, —O—CO—NR^H—, —NR^H—CO—CH₂—, —O—CH₂—CO—NR^H—, —O—CH₂—CH₂—NR^H—, CO—NR^H—CH₂—, —CH₂—NR^HCO—, —O—CH₂—CH₂—S—, —S—CH₂—CH₂—O—, —S—CH₂—CH₂—S—, —CH₂—SO₂—CH₂—, —CH₂—CO—NR^H—, —O—CH₂—CH₂—NR^H—CO—, —CH₂—NCH₃—O—CH₂—, where R^H is selected from hydrogen and C1-4-alkyl.
• Nuclease resistant linkages, such as phosphothioate linkages, are particularly useful in oligonucleotide regions capable of recruiting nuclease when forming a duplex with the target nucleic acid, such as region G for gapmers, or the non-modified nucleoside region of headmers and tailmers. Phosphorothioate linkages may, however, also be useful in non-nuclease recruiting regions and/or affinity enhancing regions such as regions F and F′ for gapmers, or the modified nucleoside region of headmers and tailmers.
• Each of the design regions may however comprise internucleoside linkages other than phosphorothioate, such as phosphodiester linkages, in particularly in regions where modified nucleosides, such as LNA, protect the linkage against nuclease degradation. Inclusion of phosphodiester linkages, such as one or two linkages, particularly between or adjacent to modified nucleoside units (typically in the non-nuclease recruiting regions) can modify the bioavailability and/or bio-distribution of an oligonucleotide—see WO2008/113832, incorporated herein by reference.
• In an embodiment all the internucleoside linkages in the oligonucleotide are phosphorothioate and/or boranophosphate linkages. Preferably, all the internucleoside linkages in the oligonucleotide are phosphorothioate linkages.
Nucleobase
• The term nucleobase includes the purine (e.g. adenine and guanine) and pyrimidine (e.g. uracil, thymine and cytosine) moiety present in nucleosides and nucleotides which form hydrogen bonds in nucleic acid hybridization. In the context of the present invention the term nucleobase also encompasses modified nucleobases which may differ from naturally occurring nucleobases, but are functional during nucleic acid hybridization. In this context “nucleobase” refers to both naturally occurring nucleobases such as adenine, guanine, cytosine, thymidine, uracil, xanthine and hypoxanthine, as well as non-naturally occurring variants. Such variants are for example described in Hirao et al (2012) Accounts of Chemical Research vol 45 page 2055 and Bergstrom (2009) Current Protocols in Nucleic Acid Chemistry Suppl. 37 1.4.1.
• In a some embodiments the nucleobase moiety is modified by changing the purine or pyrimidine into a modified purine or pyrimidine, such as substituted purine or substituted pyrimidine, such as a nucleobased selected from isocytosine, pseudoisocytosine, 5-methyl cytosine, 5-thiozolo-cytosine, 5-propynyl-cytosine, 5-propynyl-uracil, 5-bromouracil 5-thiazolo-uracil, 2-thio-uracil, 2′thio-thymine, inosine, diaminopurine, 6-aminopurine, 2-aminopurine, 2,6-diaminopurine and 2-chloro-6-aminopurine.
• The nucleobase moieties may be indicated by the letter code for each corresponding nucleobase, e.g. A, T, G, C or U, wherein each letter may optionally include modified nucleobases of equivalent function. For example, in the exemplified oligonucleotides, the nucleobase moieties are selected from A, T, G, C, and 5-methyl cytosine. Optionally, for LNA gapmers, 5-methyl cytosine LNA nucleosides may be used.
Modified Oligonucleotide
• The term modified oligonucleotide describes an oligonucleotide comprising one or more sugar-modified nucleosides and/or modified internucleoside linkages. The term chimeric” oligonucleotide is a term that has been used in the literature to describe oligonucleotides with modified nucleosides.
Complementarity
• The term complementarity describes the capacity for Watson-Crick base-pairing of nucleosides/nucleotides. Watson-Crick base pairs are guanine (G)-cytosine (C) and adenine (A)-thymine (T)/uracil (U). It will be understood that oligonucleotides may comprise nucleosides with modified nucleobases, for example 5-methyl cytosine is often used in place of cytosine, and as such the term complementarity encompasses Watson Crick base-paring between non-modified and modified nucleobases (see for example Hirao et al (2012) Accounts of Chemical Research vol 45 page 2055 and Bergstrom (2009) Current Protocols in Nucleic Acid Chemistry Suppl. 37 1.4.1).
• The term “% complementary” as used herein, refers to the number of nucleotides in percent of a contiguous nucleotide sequence in a nucleic acid molecule (e.g. oligonucleotide) which, at a given position, are complementary to (i.e. form Watson Crick base pairs with) a contiguous nucleotide sequence, at a given position of a separate nucleic acid molecule (e.g. the target nucleic acid). The percentage is calculated by counting the number of aligned bases that form pairs between the two sequences, dividing by the total number of nucleotides in the oligonucleotide and multiplying by 100. In such a comparison a nucleobase/nucleotide which does not align (form a base pair) is termed a mismatch.
• The term “fully complementary”, refers to 100% complementarity.
Hybridization
• The term “hybridizing” or “hybridizes” as used herein is to be understood as two nucleic acid strands (e.g. an oligonucleotide and a target nucleic acid) forming hydrogen bonds between base pairs on opposite strands thereby forming a duplex. The affinity of the binding between two nucleic acid strands is the strength of the hybridization. It is often described in terms of the melting temperature (T_m) defined as the temperature at which half of the oligonucleotides are duplexed with the target nucleic acid. At physiological conditions T_m is not strictly proportional to the affinity (Mergny and Lacroix, 2003, Oligonucleotides 13:515-537). The standard state Gibbs free energy ΔG° is a more accurate representation of binding affinity and is related to the dissociation constant (K_d) of the reaction by ΔG°=−RTln(K_d), where R is the gas constant and T is the absolute temperature. Therefore, a very low ΔG° of the reaction between an oligonucleotide and the target nucleic acid reflects a strong hybridization between the oligonucleotide and target nucleic acid. ΔG° is the energy associated with a reaction where aqueous concentrations are 1M, the pH is 7, and the temperature is 37° C. The hybridization of oligonucleotides to a target nucleic acid is a spontaneous reaction and for spontaneous reactions ΔG° is less than zero. ΔG° can be measured experimentally, for example, by use of the isothermal titration calorimetry (ITC) method as described in Hansen et al., 1965, Chem. Comm. 36-38 and Holdgate et al., 2005, Drug Discov Today. The skilled person will know that commercial equipment is available for ΔG° measurements. ΔG° can also be estimated numerically by using the nearest neighbor model as described by SantaLucia, 1998, Proc Natl Acad Sci USA. 95: 1460-1465 using appropriately derived thermodynamic parameters described by Sugimoto et al., 1995, Biochemistry 34:11211-11216 and McTigue et al., 2004, Biochemistry 43:5388-5405. In order to have the possibility of modulating its intended nucleic acid target by hybridization, oligonucleotides of the present invention hybridize to a target nucleic acid with estimated ΔG° values below −10 kcal for oligonucleotides that are 10-30 nucleotides in length. In some embodiments the degree or strength of hybridization is measured by the standard state Gibbs free energy ΔG°. The oligonucleotides may hybridize to a target nucleic acid with estimated ΔG° values below the range of −10 kcal, such as below −15 kcal, such as below −20 kcal and such as below −25 kcal for oligonucleotides that are 8-30 nucleotides in length. In some embodiments the oligonucleotides hybridize to a target nucleic acid with an estimated ΔG° value of −10 to −60 kcal, such as −12 to −40, such as from −15 to −30 kcal or −16 to −27 kcal such as −18 to −25 kcal.
The Target
• The target refers to the protein which it is desired to modulate.
Target Nucleic Acid
• A target nucleic acid is the intended target which the oligonucleotide of the invention hybridizes to, and may for example be a gene, a RNA, a non-coding RNA, a long non-coding RNA, a mRNA, and pre-mRNA, a mature mRNA or a cDNA sequence. In some embodiments the target nucleic acid is a non-coding RNA or a long non-coding RNA, or a subsequence thereof. For in vivo or in vitro application, the oligonucleotide of the invention is capable of decreasing the level of the SNHG14 transcript downstream of SNORD109B of and thereby relieving the suppression of the paternal UBE3A transcript in the intended target cell. The contiguous sequence of nucleobases of the oligonucleotide of the invention is complementary to the target nucleic acid, as measured across the length of the oligonucleotide, optionally with the exception of one or two mismatches, and optionally excluding nucleotide based linker regions which may link the oligonucleotide to an optional functional group such as a conjugate.
Target Sequence
• The oligonucleotide comprises a contiguous nucleotide sequence which is complementary to or hybridizes to a sub-sequence of the target nucleic acid molecule. The term “target sequence” as used herein refers to a sequence of nucleotides present in the target nucleic acid which comprises the nucleobase sequence which is complementary to the oligonucleotide of the invention. In some embodiments, the target sequence consists of a region on the target nucleic acid which is complementary to the contiguous nucleotide sequence of the oligonucleotide of the invention. In some embodiments the target sequence is longer than the complementary sequence of a single oligonucleotide, and may, for example represent a preferred region of the target nucleic acid which may be targeted by several oligonucleotides of the invention.
• The oligonucleotide of the invention comprises a contiguous nucleotide sequence which is complementary to the target nucleic acid, such as a target sequence.
• The oligonucleotide comprises a contiguous nucleotide sequence of at least 8 nucleotides which is complementary to or hybridizes to a target sequence present in the target nucleic acid molecule. The contiguous nucleotide sequence (and therefore the target sequence) comprises of at least 8 contiguous nucleotides, such as 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 contiguous nucleotides, such as from 12-25, such as from 14-18 contiguous nucleotides.
Target Cell
• The term a target cell as used herein refers to a cell which is expressing the target nucleic acid. In some embodiments the target cell may be in vivo or in vitro. In some embodiments the target cell is a mammalian cell such as a rodent cell, such as a mouse cell or a rat cell, or a primate cell such as a monkey cell or a human cell. In preferred embodiments the target cell is a neuronal cell.
Naturally Occurring Variant
• The term “naturally occurring variant” refers to variants of SNHG14 transcript downstream of SNORD109B gene or transcripts which originate from the same genetic loci as the target nucleic acid, but may differ for example, by virtue of degeneracy of the genetic code causing a multiplicity of codons in the long non-coding RNA. The oligonucleotide of the invention may therefore be designed to target the target nucleic acid and naturally occurring variants thereof.
Modulation of Expression
• The term “modulation of expression” as used herein is to be understood as an overall term for an oligonucleotide's ability to alter the amount of UBE3A protein when compared to the amount of UBE3A before administration of the oligonucleotide. Alternatively modulation of expression may be determined by reference to a control experiment where the oligonucleotide of the invention is not administered. The modulation effected by the oligonucleotide is related to it's ability to reduce, remove, prevent, lessen, lower or terminate the suppression of the paternal UBE3A transcript, e.g. by degradation or removal of the non-coding SNHG14 transcript downstream of SNORD109B or by blockage or prevention of polymerase activity associated with the SNHG14 transcript downstream of SNORD109B. The modulation can also be viewed as the oligonucleotide's ability to restore, increase or enhance expression of paternal UBE3A, e.g. by removal or blockage of inhibitory mechanisms affected by the non-coding SNHG14 transcript downstream of SNORD109B.
High Affinity Modified Nucleosides
• A high affinity modified nucleoside is a modified nucleotide which, when incorporated into the oligonucleotide enhances the affinity of the oligonucleotide for its complementary target, for example as measured by the melting temperature (T^m). A high affinity modified nucleoside of the present invention preferably result in an increase in melting temperature between +0.5 to +12° C., more preferably between +1.5 to +10° C. and most preferably between +3 to +8° C. per modified nucleoside. Numerous high affinity modified nucleosides are known in the art and include for example, many 2′ substituted nucleosides as well as locked nucleic acids (LNA) (see e.g. Freier & Altmann; Nucl. Acid Res., 1997, 25, 4429-4443 and Uhlmann; Curr. Opinion in Drug Development, 2000, 3(2), 293-213).
Sugar Modifications
• The oligomer of the invention may comprise one or more nucleosides which have a modified sugar moiety, i.e. a modification of the sugar moiety when compared to the ribose sugar moiety found in DNA and RNA.
• Numerous nucleosides with modification of the ribose sugar moiety have been made, primarily with the aim of improving certain properties of oligonucleotides, such as affinity and/or nuclease resistance.
• Such modifications include those where the ribose ring structure is modified, e.g. by replacement with a hexose ring (HNA), or a bicyclic ring, which typically have a biradicle bridge between the C2 and C4 carbons on the ribose ring (LNA), or an unlinked ribose ring which typically lacks a bond between the C2 and C3 carbons (e.g. UNA). Other sugar modified nucleosides include, for example, bicyclohexose nucleic acids (WO2011/017521) or tricyclic nucleic acids (WO2013/154798). Modified nucleosides also include nucleosides where the sugar moiety is replaced with a non-sugar moiety, for example in the case of peptide nucleic acids (PNA), or morpholino nucleic acids.
• Sugar modifications also include modifications made via altering the substituent groups on the ribose ring to groups other than hydrogen, or the 2′-OH group naturally found in DNA and RNA nucleosides. Substituents may, for example be introduced at the 2′, 3′, 4′ or 5′ positions. Nucleosides with modified sugar moieties also include 2′ modified nucleosides, such as 2′ substituted nucleosides. Indeed, much focus has been spent on developing 2′ substituted nucleosides, and numerous 2′ substituted nucleosides have been found to have beneficial properties when incorporated into oligonucleotides, such as enhanced nucleoside resistance and enhanced affinity.
2′ Modified Nucleosides.
• A 2′ sugar modified nucleoside is a nucleoside which has a substituent other than H or —OH at the 2′ position (2′ substituted nucleoside) or comprises a 2′ linked biradicle, and includes 2′ substituted nucleosides and LNA (2′-4′ biradicle bridged) nucleosides. For example, the 2′ modified sugar may provide enhanced binding affinity and/or increased nuclease resistance to the oligonucleotide. Examples of 2′ substituted modified nucleosides are 2′-O-alkyl-RNA, 2′-O-methyl-RNA, 2′-alkoxy-RNA, 2′-O-methoxyethyl-RNA (MOE), 2′-amino-DNA, 2′-Fluoro-RNA, and 2′-fluoro-ANA (F-ANA). For further examples, please see e.g. Freier & Altmann; Nucl. Acid Res., 1997, 25, 4429-4443 and Uhlmann; Curr. Opinion in Drug Development, 2000, 3(2), 293-213; and Deleavey and Damha, Chemistry and Biology 2012, 19, 937. Below are illustrations of some 2′ substituted modified nucleosides.
• 
Locked Nucleic Acid Nucleosides (LNA).
• LNA nucleosides are modified nucleosides which comprise a linker group (referred to as a biradicle or a bridge) between C2′ and C4′ of the ribose sugar ring of a nucleotide. These nucleosides are also termed bridged nucleic acid or bicyclic nucleic acid (BNA) in the literature.
• In some embodiments, the modified nucleoside or the LNA nucleosides of the oligomer of the invention has a general structure of the formula I or II:
• 
• wherein W is selected from —O—, —S—, —N(R^a)—, —C(R^aR^b)—, such as, in some embodiments —O—;
  B designates a nucleobase or modified nucleobase moiety;
  Z designates an internucleoside linkage to an adjacent nucleoside, or a 5′-terminal group;
  Z* designates an internucleoside linkage to an adjacent nucleoside, or a 3′-terminal group;
  X designates a group selected from the list consisting of —C(R^aR^b)—, —C(R^a)═C(R^b)—, —C(R^a)═N—, —O—, —Si(R^a)₂—, —S—, —SO₂—, —N(R^a)—, and >C═Z
• • In some embodiments, X is selected from the group consisting of: —O—, —S—, NH—, NR^aR^b, —CH₂—, CR^aR^b, —C(═CH₂)—, and —C(═CR^aR^b)—
  • In some embodiments, X is —O—
    Y designates a group selected from the group consisting of —C(R^aR^b)—, —C(R^a)═C(R^b)—, —C(R^a)═N—, —O—, —Si(R^a)₂—, —S—, —SO₂—, —N(R^a)—, and >C═Z
  • In some embodiments, Y is selected from the group consisting of: —CH₂—, —C(R^aR^b)—, —CH₂CH₂—, —C(R^aR^b)—C(R^aR^b)—, —CH₂CH₂CH₂—, —C(R^aR^b)C(R^aR^b)C(R^aR^b)—, —C(R^a)═C(R^b)—, and —C(R^a)═N—
  • In some embodiments, Y is selected from the group consisting of: —CH₂—, —CHR^a—, —CHCH₃—, CR^aR^b—
    or —X—Y— together designate a bivalent linker group (also referred to as a radical) together designate a bivalent linker group consisting of 1, 2, 3 or 4 groups/atoms selected from the group consisting of —C(R^aR^b)—, —C(R^a)═C(R^b)—, —C(R^a)═N—, —O—, —Si(R^a)₂—, —S—, —SO₂—, —N(R^a)—, and >C═Z,
  • In some embodiments, —X—Y— designates a biradicle selected from the groups consisting of: —X—CH₂—, —X—CR^aR^b—, —X—CHR^a—, —X—C(HCH₃)—, —O—Y—, —O—CH₂—, —S—CH₂—, —NH—CH₂—, —O—CHCH₃—, —CH₂—O—CH₂, —O—CH(CH₃CH₃)—, —O—CH₂—CH₂—, OCH₂—CH₂—CH₂—, —O—CH₂OCH₂—, —O—NCH₂—, —C(═CH₂)—CH₂—, —NR^a—CH₂—, N—O—CH₂, —S—CR^aR^b— and —S—CHR^a—.
  • In some embodiments —X—Y— designates —O—CH₂— or —O—CH(CH₃)—.
    wherein Z is selected from —O—, —S—, and —N(R^a)—,
    and R^a and, when present R^b, each is independently selected from hydrogen, optionally substituted C_1-6-alkyl, optionally substituted C_2-6-alkenyl, optionally substituted C_2-6-alkynyl, hydroxy, optionally substituted C_1-6-alkoxy, C_2-6-alkoxyalkyl, C_2-6-alkenyloxy, carboxy, C_1-6-alkoxycarbonyl, C_1-6-alkylcarbonyl, formyl, aryl, aryloxy-carbonyl, aryloxy, arylcarbonyl, heteroaryl, heteroaryloxy-carbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono- and di(C_1-6-alkyl)amino, carbamoyl, mono- and di(C_1-6-alkyl)-amino-carbonyl, amino-C_1-6-alkyl-aminocarbonyl, mono- and di(C_1-6-alkyl)amino-C_1-6-alkyl-aminocarbonyl, C_1-6-alkyl-carbonylamino, carbamido, C_1-6-alkanoyloxy, sulphono, C_1-6-alkylsulphonyloxy, nitro, azido, sulphanyl, C_1-6-alkylthio, halogen, where aryl and heteroaryl may be optionally substituted and where two geminal substituents R^a and R^b together may designate optionally substituted methylene (═CH₂), wherein for all chiral centers, asymmetric groups may be found in either R or S orientation.
    wherein R¹, R², R³, R⁵ and R^5* are independently selected from the group consisting of: hydrogen, optionally substituted C_1-6-alkyl, optionally substituted C_2-6-alkenyl, optionally substituted C_2-6-alkynyl, hydroxy, C_1-6-alkoxy, C_2-6-alkoxyalkyl, C_2-6-alkenyloxy, carboxy, C_1-6-alkoxycarbonyl, C_1-6-alkylcarbonyl, formyl, aryl, aryloxy-carbonyl, aryloxy, arylcarbonyl, heteroaryl, heteroaryloxy-carbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono- and di(C_1-6-alkyl)amino, carbamoyl, mono- and di(C_1-6-alkyl)-amino-carbonyl, amino-C_1-6-alkyl-aminocarbonyl, mono- and di(C_1-6-alkyl)amino-C_1-6-alkyl-aminocarbonyl, C_1-6-alkyl-carbonylamino, carbamido, C_1-6-alkanoyloxy, sulphono, C_1-6-alkylsulphonyloxy, nitro, azido, sulphanyl, C_1-6-alkylthio, halogen, where aryl and heteroaryl may be optionally substituted, and where two geminal substituents together may designate oxo, thioxo, imino, or optionally substituted methylene.
  • In some embodiments R¹, R², R³, R⁵ and R^5* are independently selected from C_1-6 alkyl, such as methyl, and hydrogen.
  • In some embodiments R¹, R², R³, R⁵ and R^5* are all hydrogen.
  • In some embodiments R¹, R², R³, are all hydrogen, and either R⁵ and R^5* is also hydrogen and the other of R⁵ and R^5* is other than hydrogen, such as C_1-6 alkyl such as methyl.
  • In some embodiments, R^a is either hydrogen or methyl. In some embodiments, when present, R^b is either hydrogen or methyl.
  • In some embodiments, one or both of R^a and R^b is hydrogen
  • In some embodiments, one of R^a and R^b is hydrogen and the other is other than hydrogen
  • In some embodiments, one of R^a and R^b is methyl and the other is hydrogen
  • In some embodiments, both of R^a and R^b are methyl.
• In some embodiments, the biradicle —X—Y— is —O—CH₂—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such LNA nucleosides are disclosed in WO99/014226, WO00/66604, WO98/039352 and WO2004/046160 which are all hereby incorporated by reference, and include what are commonly known as beta-D-oxy LNA and alpha-L-oxy LNA nucleosides.
• In some embodiments, the biradicle —X—Y— is —S—CH₂—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such thio LNA nucleosides are disclosed in WO99/014226 and WO2004/046160 which are hereby incorporated by reference.
• In some embodiments, the biradicle —X—Y— is —NH—CH₂—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such amino LNA nucleosides are disclosed in WO99/014226 and WO2004/046160 which are hereby incorporated by reference.
• In some embodiments, the biradicle —X—Y— is —O—CH₂—CH₂— or —O—CH₂—CH₂—CH₂—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such LNA nucleosides are disclosed in WO00/047599 and Morita et al, Bioorganic & Med. Chem. Lett. 12 73-76, which are hereby incorporated by reference, and include what are commonly known as 2′-O-4′C-ethylene bridged nucleic acids (ENA).
• In some embodiments, the biradicle —X—Y— is —O—CH₂—, W is O, and all of R¹, R², R³, and one of R⁵ and R^5* are hydrogen, and the other of R⁵ and R^5* is other than hydrogen such as C_1-6 alkyl, such as methyl. Such 5′ substituted LNA nucleosides are disclosed in WO2007/134181 which is hereby incorporated by reference.
• In some embodiments, the biradicle —X—Y— is —O—CR^aR^b—, wherein one or both of R^a and R^b are other than hydrogen, such as methyl, W is O, and all of R¹, R², R³, and one of R⁵ and R^5* are hydrogen, and the other of R⁵ and R^5* is other than hydrogen such as C_1-6 alkyl, such as methyl. Such bis modified LNA nucleosides are disclosed in WO2010/077578 which is hereby incorporated by reference.
• In some embodiments, the biradicle —X—Y— designate the bivalent linker group —O—CH(CH₂OCH₃)— (2′ O-methoxyethyl bicyclic nucleic acid—Seth at al., 2010, J. Org. Chem. Vol 75(5) pp. 1569-81). In some embodiments, the biradicle —X—Y— designate the bivalent linker group —O—CH(CH₂CH₃)-(2′O-ethyl bicyclic nucleic acid—Seth at al., 2010, J. Org. Chem. Vol 75(5) pp. 1569-81). In some embodiments, the biradicle —X—Y— is —O—CHR^a—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such 6′ substituted LNA nucleosides are disclosed in WO10036698 and WO07090071 which are both hereby incorporated by reference.
• In some embodiments, the biradicle —X—Y— is —O—CH(CH₂OCH₃)—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such LNA nucleosides are also known as cyclic MOEs in the art (cMOE) and are disclosed in WO07090071.
• In some embodiments, the biradicle —X—Y— designate the bivalent linker group —O—CH(CH₃)—.—in either the R- or S-configuration. In some embodiments, the biradicle —X—Y— together designate the bivalent linker group —O—CH₂—O—CH₂— (Seth at al., 2010, J. Org. Chem). In some embodiments, the biradicle —X—Y— is —O—CH(CH₃)—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such 6′ methyl LNA nucleosides are also known as cET nucleosides in the art, and may be either (S)cET or (R)cET stereoisomers, as disclosed in WO07090071 (beta-D) and WO2010/036698 (alpha-L) which are both hereby incorporated by reference).
• In some embodiments, the biradicle —X—Y— is —O—CR^aR^b—, wherein in neither R^a or R^b is hydrogen, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some embodiments, R^a and R^b are both methyl. Such 6′ di-substituted LNA nucleosides are disclosed in WO 2009006478 which is hereby incorporated by reference.
• In some embodiments, the biradicle —X—Y— is —S—CHR^a—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such 6′ substituted thio LNA nucleosides are disclosed in WO11156202 which is hereby incorporated by reference. In some 6′ substituted thio LNA embodiments R^a is methyl.
• In some embodiments, the biradicle —X—Y— is —C(═CH₂)—C(R^aR^b)—, such as —C(═CH₂)—CH₂—, or —C(═CH₂)—CH(CH₃)—W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. Such vinyl carbo LNA nucleosides are disclosed in WO08154401 and WO09067647 which are both hereby incorporated by reference.
• In some embodiments the biradicle —X—Y— is —N(—OR^a)—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some embodiments R^a is C_1-6 alkyl such as methyl. Such LNA nucleosides are also known as N substituted LNAs and are disclosed in WO2008/150729 which is hereby incorporated by reference. In some embodiments, the biradicle —X—Y— together designate the bivalent linker group —O—NR^a—CH₃— (Seth at al., 2010, J. Org. Chem). In some embodiments the biradicle —X—Y— is —N(R^a)—, W is O, and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some embodiments R^a is C_1-6 alkyl such as methyl.
• In some embodiments, one or both of R⁵ and R^5* is hydrogen and, when substituted the other of R⁵ and R^5* is C_1-6 alkyl such as methyl. In such an embodiment, R¹, R², R³, may all be hydrogen, and the biradicle —X—Y— may be selected from —O—CH2- or —O—C(HCR^a)—, such as —O—C(HCH3)-.
• In some embodiments, the biradicle is —CR^aR^b—O—CR^aR^b—, such as CH₂—O—CH₂—, W is O and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some embodiments R^a is C_1-6 alkyl such as methyl. Such LNA nucleosides are also known as conformationally restricted nucleotides (CRNs) and are disclosed in WO2013036868 which is hereby incorporated by reference.
• In some embodiments, the biradicle is —O—CR^aR^b—O—CR^aR^b—, such as O—CH₂—O—CH₂—, W is O and all of R¹, R², R³, R⁵ and R^5* are all hydrogen. In some embodiments R^a is C_1-6 alkyl such as methyl. Such LNA nucleosides are also known as COC nucleotides and are disclosed in Mitsuoka et al., Nucleic Acids Research 2009 37(4), 1225-1238, which is hereby incorporated by reference.
• It will be recognized than, unless specified, the LNA nucleosides may be in the beta-D or alpha-L stereoisoform.
• Certain examples of LNA nucleosides are presented in Scheme 1.
• 
• As illustrated in the examples, in preferred embodiments of the invention the LNA nucleosides in the oligonucleotides are beta-D-oxy-LNA nucleosides.
Nuclease Mediated Degradation
• Nuclease mediated degradation refers to an oligonucleotide capable of mediating degradation of a complementary nucleotide sequence when forming a duplex with such a sequence.
• In some embodiments, the oligonucleotide may function via nuclease mediated degradation of the target nucleic acid, where the oligonucleotides of the invention are capable of recruiting a nuclease, particularly and endonuclease, preferably endoribonuclease (RNase), such as RNase H. Examples of oligonucleotide designs which operate via nuclease mediated mechanisms are oligonucleotides which typically comprise a region of at least 5 or 6 DNA nucleosides and are flanked on one side or both sides by affinity enhancing nucleosides, for example gapmers, headmers and tailmers.
RNase H Activity and Recruitment
• The RNase H activity of an antisense oligonucleotide refers to its ability to recruit RNase H when in a duplex with a complementary RNA molecule. WO01/23613 provides in vitro methods for determining RNaseH activity, which may be used to determine the ability to recruit RNaseH. Typically an oligonucleotide is deemed capable of recruiting RNase H if it, when provided with a complementary target nucleic acid sequence, has an initial rate, as measured in pmol/l/min, of at least 10% or more than 20% of the of the initial rate determined when using a oligonucleotide having the same base sequence as the modified oligonucleotide being tested, but containing only DNA monomers, with phosphorothioate linkages between all monomers in the oligonucleotide, and using the methodology provided by Example 91-95 of WO01/23613 (hereby incorporated by reference).
Gapmer
• The term gapmer as used herein refers to an antisense oligonucleotide which comprises a region of RNase H recruiting oligonucleotides (gap) which is flanked 5′ and 3′ by one or more affinity enhancing modified nucleosides (flanks). Various gapmer designs are described herein. Headmers and tailmers are oligonucleotides capable of recruiting RNase H where one of the flanks is missing, i.e. only one of the ends of the oligonucleotide comprises affinity enhancing modified nucleosides. For headmers the 3′ flank is missing (i.e. the 5′ flanc comprise affinity enhancing modified nucleosides) and for tailmers the 5′ flank is missing (i.e. the 3′ flank comprises affinity enhancing modified nucleosides).
LNA Gapmer
• The term LNA gapmer is a gapmer oligonucleotide wherein at least one of the affinity enhancing modified nucleosides is an LNA nucleoside.
Mixed Wing Gapmer
• The term mixed wing gapmer refers to a LNA gapmer wherein the flank regions comprise at least one LNA nucleoside and at least one non-LNA modified nucleoside, such as at least one 2′ substituted modified nucleoside, such as, for example, 2′-O-alkyl-RNA, 2′-O-methyl-RNA, 2′-alkoxy-RNA, 2′-O-methoxyethyl-RNA (MOE), 2′-amino-DNA, 2′-Fluoro-RNA, and 2′-F-ANA nucleoside(s). In some embodiments the mixed wing gapmer has one flank which comprises LNA nucleosides (e.g. 5′ or 3′) and the other flank (3′ or 5′ respectfully) comprises 2′ substituted modified nucleoside(s).
Conjugate
• The term conjugate as used herein refers to an oligonucleotide which is covalently linked to a non-nucleotide moiety (conjugate moiety or region C or third region).
• Conjugation of the oligonucleotide of the invention to one or more non-nucleotide moieties may improve the pharmacology of the oligonucleotide, e.g. by affecting the activity, cellular distribution, cellular uptake or stability of the oligonucleotide. In some embodiments the conjugate moiety modify or enhance the pharmacokinetic properties of the oligonucleotide by improving cellular distribution, bioavailability, metabolism, excretion, permeability, and/or cellular uptake of the oligonucleotide. In particular the conjugate may target the oligonucleotide to a specific organ, tissue or cell type and thereby enhance the effectiveness of the oligonucleotide in that organ, tissue or cell type. A the same time the conjugate may serve to reduce activity of the oligonucleotide in non-target cell types, tissues or organs, e.g. off target activity or activity in non-target cell types, tissues or organs. WO 93/07883 and WO 2013/033230 provides suitable conjugate moieties, which are hereby incorporated by reference. WO 2012/143379 provides a method of delivering a drug across the blood-brain-barrier by conjugation to an antibody fragment with affinity to the transferrin receptor, which are hereby incorporated by reference.
• Oligonucleotide conjugates and their synthesis has also been reported in comprehensive reviews by Manoharan in Antisense Drug Technology, Principles, Strategies, and Applications, S. T. Crooke, ed., Ch. 16, Marcel Dekker, Inc., 2001 and Manoharan, Antisense and Nucleic Acid Drug Development, 2002, 12, 103, each of which is incorporated herein by reference in its entirety.
• In an embodiment, the non-nucleotide moiety (conjugate moiety) is selected from the group consisting of carbohydrates, cell surface receptor ligands, drug substances, hormones, lipophilic substances, polymers, proteins, peptides, toxins (e.g. bacterial toxins), vitamins, viral proteins (e.g. capsids) or combinations thereof. In some embodiments the non-nucleotide moiety an antibody or antibody fragment, such as an antibody or antibody fragment that facilitates delivery across the blood-brain-barrier, in particular an antibody or antibody fragment targeting the transferrin receptor.
Linkers
• A linkage or linker is a connection between two atoms that links one chemical group or segment of interest to another chemical group or segment of interest via one or more covalent bonds. Conjugate moieties can be attached to the oligonucleotide directly or through a linking moiety (e.g. linker or tether). Linkers serve to covalently connect a third region, e.g. a conjugate moiety (Region C), to a first region, e.g. an oligonucleotide (region A).
• In some embodiments of the invention the conjugate or oligonucleotide conjugate of the invention may optionally, comprise a linker region (second region or region B and/or region Y) which is positioned between the oligonucleotide (region A or first region) and the conjugate moiety (region C or third region).
• Region B refers to biocleavable linkers comprising or consisting of a physiologically labile bond that is cleavable under conditions normally encountered or analogous to those encountered within a mammalian body. Conditions under which physiologically labile linkers undergo chemical transformation (e.g., cleavage) include chemical conditions such as pH, temperature, oxidative or reductive conditions or agents, and salt concentration found in or analogous to those encountered in mammalian cells. Mammalian intracellular conditions also include the presence of enzymatic activity normally present in a mammalian cell such as from proteolytic enzymes or hydrolytic enzymes or nucleases. In one embodiment the biocleavable linker is susceptible to S1 nuclease cleavage. In a preferred embodiment the nuclease susceptible linker comprises between 1 and 10 nucleosides, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleosides, more preferably between 2 and 6 nucleosides and most preferably between 2 and 4 linked nucleosides comprising at least two consecutive phosphodiester linkages, such as at least 3 or 4 or 5 consecutive phosphodiester linkages. Preferably the nucleosides are DNA or RNA. Phosphodiester containing biocleavable linkers are described in more detail in WO 2014/076195 (hereby incorporated by reference).
• Region Y refers to linkers that are not necessarily biocleavable but primarily serve to covalently connect a conjugate moiety (region C or third region), to an oligonucleotide (region A or first region). The region Y linkers may comprise a chain structure or an oligomer of repeating units such as ethylene glycol, amino acid units or amino alkyl groups The oligonucleotide conjugates of the present invention can be constructed of the following regional elements A-C, A-B-C, A-B-Y-C, A-Y-B-C or A-Y-C. In some embodiments the linker (region Y) is an amino alkyl, such as a C2-C36 amino alkyl group, including, for example C6 to C12 amino alkyl groups. In a preferred embodiment the linker (region Y) is a C6 amino alkyl group.
Control
• By the term “control” when used in relation to measurements of the effect of an oligonucleotide it is generally understood that the control is an untreated individual or target cell or a individual or target cell treated with a non-targeting oligonucleotide (mock). It may however also be an individual treated with the standard of care.
Treatment
• The term ‘treatment’ as used herein refers to both treatment of an existing disease (e.g. a disease or disorder as herein referred to), or prevention of a disease, i.e. prophylaxis. It will therefore be recognized that treatment as referred to herein may, in some embodiments, be prophylactic.
DETAILED DESCRIPTION OF THE INVENTION The Target
• An aspect of the invention is to modulate the level of pig, primate or human UBE3A protein expression, in particular to increase the expression of paternal UBE3A expression in neuronal cells, in particular in human neuronal cells. The human UBE3A protein exists in several isoforms which are listed under Uniprot nr. Q05086. Several mutations in the maternal UBE3A gene can results in Angelman syndrome.
• The target nucleic acid for the oligonucleotides of the invention is RNA, in particular a long non-coding RNA. The long non-coding RNA which is targeted by the oligonucleotides of the present invention is human SNHG14 (also known as UBE3A-ATS with Ensembl entry number ENSG00000224078, version GRCh38.p2). In particular the target nucleic acid is the region downstream of SNORD109B corresponding to position 25278410 to 25419462 on chromosome 15 (SEQ ID NO: 1). In Rhesus monkey (Macaca mulatta) the UBE3A suppressor is defined as region downstream of SNORD109A corresponding to position 4222848 to U.S. Pat. No. 4,373,084 (forward strand) on chromosome 7 using the Ensembl assembly MMUL 1.0 (SEQ ID NO: 2).
• In some embodiments, the target nucleic acid is SEQ ID NO: 1, or naturally occurring variants thereof.
• In certain embodiments the target nucleic acid correspond to regions which are conserved between human (SEQ ID NO: 1) and Rhesus monkey (SEQ ID NO: 2). In certain embodiments target nucleic acid correspond to regions which are conserved between human (SEQ ID NO:1), Rhesus monkey (SEQ ID NO: 2) and mouse (SEQ ID NO: 3).
• In certain embodiments the target nucleic acid is the region that is antisense to the UBE3A pre-mRNA, this region corresponds to position 55319 to 141053 of SEQ ID NO: 1.
• In certain embodiments the target nucleic acid is the region that is downstream of SNORD109B and upstream of the region that is antisense to the UBE3A pre-mRNA, this region corresponds to position 1 to 55319 of SEQ ID NO: 1.
• In some embodiments, the target nucleic acid is present in a cell, such as a mammalian cell in particular a human cell in vitro or in vivo (the target cell). In certain embodiments the target cell is a neuron, preferably a human neuronal cell.
• The target sequence may be a sub-sequence of the target nucleic acid. In some embodiments the oligonucleotide targets sub-sequence selected from the group consisting of the antisense region of exon 9, exon10, exon13, exon14, intron 14, exon 15, intron15 and exon 16 of UBE3A. In some embodiments the oligonucleotide or contiguous nucleotide sequence hybridize or is complementary to a single stranded nucleic acid molecule selected from the group consisting of positions: 55319-76274, 77483-77573, 92157-93403 and 97056-97354 of SEQ ID NO: 1. In some embodiments the oligonucleotide or contiguous nucleotide sequence hybridize or is complementary to a single stranded nucleic acid molecule selected from the group consisting of positions: 60821-60849, 77567-77583, 92323-92339 and 97156-97172 of SEQ ID NO: 1.
• In some embodiments the target nucleic acid is a region corresponding to positions 9200-9250 of SEQ ID NO: 1.
• In some embodiments the target nucleic acid is a region corresponding to positions 11505-11555 of SEQ ID NO: 1.
• In some embodiments the target nucleic acid is a region corresponding to positions 15100-15150 of SEQ ID NO: 1.
• In some embodiments the target nucleic acid is a region corresponding to positions 30590-30740 of SEQ ID NO: 1.
• In some embodiments the target nucleic acid is a region corresponding to positions 46380-46430 of SEQ ID NO: 1.
The Oligonucleotides of the Invention
• The invention relates to oligonucleotides capable of modulating expression of paternal UBE3A, in particular induction or up-regulation of paternally expressed UBE3A in neuronal cells. The modulation is achieved by hybridizing to a target nucleic acid located on the long non-coding RNA SNHG14 transcript downstream of SNORD109B. In certain embodiments the oligonucleotide of the invention hybridizes to a sub-sequence of the target nucleic acid of SEQ ID NO: 1 with a ΔG° below −10 kcal, such as with a ΔG° between −10 to −60 kcal, such as −12 to −40, such as from −15 to −30 kcal or −16 to −27 kcal such as −18 to −25 kcal.
• The oligonucleotide of the invention is an antisense oligonucleotide which targets the pig, rhesus monkey and/or human SNHG14 transcript downstream of SNORD109B.
• In some embodiments the antisense oligonucleotide of the invention is capable of modulating the expression of the target by removing, interfering with or decreasing the suppressor of the target. Preferably, the oligonucleotides of the invention induce UBE3A expression in a cell, in particular paternal UBE3A expression in a neuron, by degradation or removal of the SNHG14 transcript downstream of SNORD109B. In some embodiments the oligonucleotides of the invention are capable of increasing the expression of UBE3A by least 20% compared to the expression level of UBE3A in a neuronal cell treated with saline or a non-targeting oligonucleotide, more preferably by at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 80%, 100%, 120%, 150%, 160%, 170%, 180%, 190%, 200%, 210%, 220%, 230%, 240% or 250% compared to the expression level of UBE3A in a neuronal cell treated with saline or a non-targeting oligonucleotide. In additional embodiments the oligonucleotides of the invention are capable of decreasing the level of the SNHG14 transcript downstream of SNORD109B (in particular the part of the transcript that is antisense to the UBE3A pre-mRNA region) by at least 20% compared to the level of the SNHG14 transcript downstream of SNORD109B in a neuronal cell treated with saline or a non-targeting oligonucleotide, more preferably by at least 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% compared to the level of the SNHG14 transcript downstream of SNORD109B in a neuronal cell treated with saline or a non-targeting oligonucleotide, without reducing SNORD115 levels by more than 0%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 25% or 30% compared to the level of SNORD115 in a cell treated with saline or a non-targeting oligonucleotide. SNRPN and SNORD116 transcripts are located upstream from the SNORD115 transcript consequently if the SNORD115 transcript is not reduced by the oligonucleotide it is highly likely that the SNRPN and SNORD116 transcripts are also not reduced. In a further embodiment SNRPN and SNORD116 transcripts levels are not reduced by more than 0%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 25% or 30% compared to the level of SNRPN and SNORD116 in a cell treated with saline or a non-targeting oligonucleotide.
• The target modulation is triggered by the hybridization between a contiguous nucleotide sequence of the oligonucleotide and the target nucleic acid. In some embodiments the oligonucleotide of the invention comprises mismatches between the oligonucleotide and the target nucleic acid. Despite mismatches hybridization to the target nucleic acid may still be sufficient to show a desired modulation of UBE3A expression. Reduced binding affinity resulting from mismatches may advantageously be compensated by increased number of nucleotides in the oligonucleotide and/or an increased number of modified nucleosides capable of increasing the binding affinity to the target, such as 2′ modified nucleosides, including LNA, present within the oligonucleotide sequence.
• An aspect of the present invention relates to an antisense oligonucleotide which comprises a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90%, such as 95%, such as 98% such as 100% complementarity to position 25278410 to 25419462 on human chromosome 15.
• In some embodiments, the oligonucleotide comprises a contiguous sequence which is at least 90% complementary, such as at least 91%, such as at least 92%, such as at least 93%, such as at least 94%, such as at least 95%, such as at least 96%, such as at least 97%, such as at least 98%, or 100% complementary with a region of the target nucleic acid shown as SEQ ID NO: 1, 2 or 3.
• In a preferred embodiment the oligonucleotide of the invention, or contiguous nucleotide sequence thereof is fully complementary (100% complementary) to a region of the target nucleic acid shown as SEQ ID NO: 1, or in some embodiments may comprise one or two mismatches between the oligonucleotide and the target nucleic acid.
• In some embodiments the oligonucleotide sequence is 100% complementary to a corresponding target nucleic acid region present in SEQ ID NO: 1 and SEQ ID NO: 2. In some embodiments the oligonucleotide sequence is 100% complementary to a corresponding target nucleic acid region present SEQ ID NO: 1, 2 and 3.
• In some embodiments, the oligonucleotide comprises a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary, such as 100% complementarity, to a corresponding target nucleic acid region present in SEQ ID NO: 1, wherein the target nucleic acid region is selected from the group consisting of region A1 to A3649 in table 1

• TABLE 1
  Regions of SEQ ID NO 1 which may be targeted
  using oligonucleotide of the invention

  	Position in
  	SEQ ID NO 1

  	Reg. A	from	to	Length

  	1	10	75	66
  	2	77	91	15
  	3	93	108	16
  	4	168	213	46
  	5	217	282	66
  	6	284	299	16
  	7	301	328	28
  	8	330	344	15
  	9	361	400	40
  	10	415	447	33
  	11	449	470	22
  	12	472	487	16
  	13	489	521	33
  	14	523	540	18
  	15	551	570	20
  	16	590	638	49
  	17	652	670	19
  	18	672	733	62
  	19	735	756	22
  	20	758	773	16
  	21	781	829	49
  	22	831	870	40
  	23	882	903	22
  	24	918	949	32
  	25	961	990	30
  	26	1007	1021	15
  	27	1019	1050	32
  	28	1052	1090	39
  	29	1092	1139	48
  	30	1147	1179	33
  	31	1175	1212	38
  	32	1220	1242	23
  	33	1245	1259	15
  	34	1265	1278	14
  	35	1285	1323	39
  	36	1317	1330	14
  	37	1337	1355	19
  	38	1357	1403	47
  	39	1405	1421	17
  	40	1423	1481	59
  	41	1486	1515	30
  	42	1521	1581	61
  	43	1611	1633	23
  	44	1631	1644	14
  	45	1635	1663	29
  	46	1669	1684	16
  	47	1685	1709	25
  	48	1711	1724	14
  	49	1726	1746	21
  	50	1754	1808	55
  	51	1819	1860	42
  	52	1862	1878	17
  	53	1896	1910	15
  	54	1923	1944	22
  	55	1946	1987	42
  	56	1985	2051	67
  	57	2053	2082	30
  	58	2088	2104	17
  	59	2106	2125	20
  	60	2132	2207	76
  	61	2209	2234	26
  	62	2247	2261	15
  	63	2263	2286	24
  	64	2290	2306	17
  	65	2308	2329	22
  	66	2347	2391	45
  	67	2398	2431	34
  	68	2447	2468	22
  	69	2470	2555	86
  	70	2565	2579	15
  	71	2579	2592	14
  	72	2589	2605	17
  	73	2594	2657	64
  	74	2672	2687	16
  	75	2692	2705	14
  	76	2703	2721	19
  	77	2770	2824	55
  	78	2826	2841	16
  	79	2838	2851	14
  	80	2843	2889	47
  	81	2896	2930	35
  	82	2930	2967	38
  	83	2965	2988	24
  	84	2984	3028	45
  	85	3024	3080	57
  	86	3081	3135	55
  	87	3140	3176	37
  	88	3168	3189	22
  	89	3197	3222	26
  	90	3212	3226	15
  	91	3221	3248	28
  	92	3243	3256	14
  	93	3250	3264	15
  	94	3266	3292	27
  	95	3326	3343	18
  	96	3345	3391	47
  	97	3400	3422	23
  	98	3424	3441	18
  	99	3434	3447	14
  	100	3443	3503	61
  	101	3495	3508	14
  	102	3505	3558	54
  	103	3589	3609	21
  	104	3611	3641	31
  	105	3662	3696	35
  	106	3698	3719	22
  	107	3723	3790	68
  	108	3810	3854	45
  	109	3858	3873	16
  	110	3902	3968	67
  	111	3971	4009	39
  	112	4005	4018	14
  	113	4011	4030	20
  	114	4032	4077	46
  	115	4082	4114	33
  	116	4123	4140	18
  	117	4150	4164	15
  	118	4166	4183	18
  	119	4185	4243	59
  	120	4248	4268	21
  	121	4284	4313	30
  	122	4317	4348	32
  	123	4364	4471	108
  	124	4473	4491	19
  	125	4494	4519	26
  	126	4521	4535	15
  	127	4545	4560	16
  	128	4567	4606	40
  	129	4616	4714	99
  	130	4725	4755	31
  	131	4757	4786	30
  	132	4788	4852	65
  	133	4856	4910	55
  	134	4912	4935	24
  	135	4937	4970	34
  	136	4972	5010	39
  	137	5058	5078	21
  	138	5080	5116	37
  	139	5110	5124	15
  	140	5135	5166	32
  	141	5168	5201	34
  	142	5203	5247	45
  	143	5261	5276	16
  	144	5278	5293	16
  	145	5314	5330	17
  	146	5332	5382	51
  	147	5398	5414	17
  	148	5427	5456	30
  	149	5458	5471	14
  	150	5487	5500	14
  	151	5506	5545	40
  	152	5561	5577	17
  	153	5580	5617	38
  	154	5607	5620	14
  	155	5619	5642	24
  	156	5644	5683	40
  	157	5685	5698	14
  	158	5713	5759	47
  	159	5756	5769	14
  	160	5784	5803	20
  	161	5801	5865	65
  	162	5873	5905	33
  	163	5907	5937	31
  	164	5939	5985	47
  	165	5987	6017	31
  	166	6016	6039	24
  	167	6028	6092	65
  	168	6102	6127	26
  	169	6127	6152	26
  	170	6151	6171	21
  	171	6178	6206	29
  	172	6217	6234	18
  	173	6224	6270	47
  	174	6272	6289	18
  	175	6291	6310	20
  	176	6312	6357	46
  	177	6367	6389	23
  	178	6396	6422	27
  	179	6440	6454	15
  	180	6456	6482	27
  	181	6484	6513	30
  	182	6505	6519	15
  	183	6518	6553	36
  	184	6552	6565	14
  	185	6557	6590	34
  	186	6596	6628	33
  	187	6640	6675	36
  	188	6686	6711	26
  	189	6714	6746	33
  	190	6781	6818	38
  	191	6832	6885	54
  	192	6889	6912	24
  	193	6920	6938	19
  	194	6940	6960	21
  	195	6954	6976	23
  	196	6998	7033	36
  	197	7035	7061	27
  	198	7071	7143	73
  	199	7159	7214	56
  	200	7253	7266	14
  	201	7268	7281	14
  	202	7283	7328	46
  	203	7329	7343	15
  	204	7338	7355	18
  	205	7345	7374	30
  	206	7374	7387	14
  	207	7383	7396	14
  	208	7389	7405	17
  	209	7399	7413	15
  	210	7420	7437	18
  	211	7427	7448	22
  	212	7450	7503	54
  	213	7495	7565	71
  	214	7561	7616	56
  	215	7618	7703	86
  	216	7717	7772	56
  	217	7776	7838	63
  	218	7852	7869	18
  	219	7882	7910	29
  	220	7919	7942	24
  	221	7944	7957	14
  	222	7959	7977	19
  	223	7979	7996	18
  	224	7998	8014	17
  	225	8030	8046	17
  	226	8059	8092	34
  	227	8100	8113	14
  	228	8115	8141	27
  	229	8143	8175	33
  	230	8179	8192	14
  	231	8187	8208	22
  	232	8205	8219	15
  	233	8210	8229	20
  	234	8231	8252	22
  	235	8254	8298	45
  	236	8302	8316	15
  	237	8306	8329	24
  	238	8331	8357	27
  	239	8400	8443	44
  	240	8443	8456	14
  	241	8445	8460	16
  	242	8472	8505	34
  	243	8494	8507	14
  	244	8554	8569	16
  	245	8571	8653	83
  	246	8659	8673	15
  	247	8675	8694	20
  	248	8696	8713	18
  	249	8736	8844	109
  	250	8847	8909	63
  	251	8915	8959	45
  	252	8961	8975	15
  	253	8993	9009	17
  	254	9024	9048	25
  	255	9050	9063	14
  	256	9089	9120	32
  	257	9127	9166	40
  	258	9191	9249	59
  	259	9257	9285	29
  	260	9288	9302	15
  	261	9331	9397	67
  	262	9399	9438	40
  	263	9437	9455	19
  	264	9483	9505	23
  	265	9507	9526	20
  	266	9583	9598	16
  	267	9600	9613	14
  	268	9628	9641	14
  	269	9653	9674	22
  	270	9676	9690	15
  	271	9745	9758	14
  	272	9752	9780	29
  	273	9796	9809	14
  	274	9811	9825	15
  	275	9832	9853	22
  	276	9877	9899	23
  	277	9901	9932	32
  	278	10000	10016	17
  	279	10029	10049	21
  	280	10051	10071	21
  	281	10089	10120	32
  	282	10111	10127	17
  	283	10122	10203	82
  	284	10211	10237	27
  	285	10239	10256	18
  	286	10258	10285	28
  	287	10287	10304	18
  	288	10306	10350	45
  	289	10352	10375	24
  	290	10381	10402	22
  	291	10412	10470	59
  	292	10474	10488	15
  	293	10508	10557	50
  	294	10565	10630	66
  	295	10632	10674	43
  	296	10698	10711	14
  	297	10701	10714	14
  	298	10704	10718	15
  	299	10720	10740	21
  	300	10742	10785	44
  	301	10786	10809	24
  	302	10811	10829	19
  	303	10832	10867	36
  	304	10869	10930	62
  	305	10932	10950	19
  	306	10959	10996	38
  	307	10998	11028	31
  	308	11037	11077	41
  	309	11079	11105	27
  	310	11115	11132	18
  	311	11134	11154	21
  	312	11156	11196	41
  	313	11206	11239	34
  	314	11241	11255	15
  	315	11266	11287	22
  	316	11299	11329	31
  	317	11331	11352	22
  	318	11358	11403	46
  	319	11405	11432	28
  	320	11434	11480	47
  	321	11482	11535	54
  	322	11539	11573	35
  	323	11584	11732	149
  	324	11731	11763	33
  	325	11765	11782	18
  	326	11784	11813	30
  	327	11815	11829	15
  	328	11831	11852	22
  	329	11854	11871	18
  	330	11866	11895	30
  	331	11930	11943	14
  	332	11975	12007	33
  	333	11996	12012	17
  	334	12017	12040	24
  	335	12050	12083	34
  	336	12088	12111	24
  	337	12133	12151	19
  	338	12161	12174	14
  	339	12179	12225	47
  	340	12238	12256	19
  	341	12265	12278	14
  	342	12296	12360	65
  	343	12362	12381	20
  	344	12384	12399	16
  	345	12400	12475	76
  	346	12487	12502	16
  	347	12504	12531	28
  	348	12533	12562	30
  	349	12564	12602	39
  	350	12627	12646	20
  	351	12655	12679	25
  	352	12681	12698	18
  	353	12700	12812	113
  	354	12828	12876	49
  	355	12877	12913	37
  	356	12932	12945	14
  	357	12936	12967	32
  	358	12988	13002	15
  	359	12996	13009	14
  	360	13018	13035	18
  	361	13031	13049	19
  	362	13056	13093	38
  	363	13096	13126	31
  	364	13128	13142	15
  	365	13144	13193	50
  	366	13201	13221	21
  	367	13223	13280	58
  	368	13282	13298	17
  	369	13300	13315	16
  	370	13307	13320	14
  	371	13315	13331	17
  	372	13351	13411	61
  	373	13422	13437	16
  	374	13439	13456	18
  	375	13461	13483	23
  	376	13485	13541	57
  	377	13543	13560	18
  	378	13574	13606	33
  	379	13618	13646	29
  	380	13778	13801	24
  	381	13994	14009	16
  	382	14508	14521	14
  	383	15049	15067	19
  	384	15069	15090	22
  	385	15102	15139	38
  	386	15142	15180	39
  	387	15182	15205	24
  	388	15238	15252	15
  	389	15254	15277	24
  	390	15292	15320	29
  	391	15322	15348	27
  	392	15343	15358	16
  	393	15362	15387	26
  	394	15399	15414	16
  	395	15416	15445	30
  	396	15459	15528	70
  	397	15537	15592	56
  	398	15610	15638	29
  	399	15640	15653	14
  	400	15655	15717	63
  	401	15719	15738	20
  	402	15757	15778	22
  	403	15783	15801	19
  	404	15818	15838	21
  	405	15835	15849	15
  	406	15840	15857	18
  	407	15856	15898	43
  	408	15900	15916	17
  	409	15931	15972	42
  	410	15988	16028	41
  	411	16030	16075	46
  	412	16103	16164	62
  	413	16207	16243	37
  	414	16233	16246	14
  	415	16255	16329	75
  	416	16349	16376	28
  	417	16378	16404	27
  	418	16399	16419	21
  	419	16421	16461	41
  	420	16463	16479	17
  	421	16481	16503	23
  	422	16506	16579	74
  	423	16582	16620	39
  	424	16622	16698	77
  	425	16700	16716	17
  	426	16723	16771	49
  	427	16786	16816	31
  	428	16835	16864	30
  	429	16865	16878	14
  	430	16872	16888	17
  	431	16890	16906	17
  	432	16904	16938	35
  	433	16965	17052	88
  	434	17054	17069	16
  	435	17071	17085	15
  	436	17083	17098	16
  	437	17088	17111	24
  	438	17124	17138	15
  	439	17140	17159	20
  	440	17181	17202	22
  	441	17202	17218	17
  	442	17229	17248	20
  	443	17250	17268	19
  	444	17332	17349	18
  	445	17363	17387	25
  	446	17389	17429	41
  	447	17450	17464	15
  	448	17482	17497	16
  	449	18104	18117	14
  	450	18418	18431	14
  	451	18613	18626	14
  	452	18620	18634	15
  	453	18707	18721	15
  	454	18841	18855	15
  	455	18875	18889	15
  	456	19282	19295	14
  	457	19310	19323	14
  	458	19454	19467	14
  	459	19774	19792	19
  	460	19794	19864	71
  	461	19862	19890	29
  	462	19892	19918	27
  	463	19907	19931	25
  	464	19927	19942	16
  	465	19932	19971	40
  	466	19973	20011	39
  	467	20022	20063	42
  	468	20080	20093	14
  	469	20131	20144	14
  	470	20240	20253	14
  	471	20448	20463	16
  	472	20495	20508	14
  	473	20532	20545	14
  	474	20600	20613	14
  	475	20617	20630	14
  	476	20960	20977	18
  	477	21412	21428	17
  	478	21465	21479	15
  	479	21489	21508	20
  	480	21797	21812	16
  	481	22015	22030	16
  	482	22144	22157	14
  	483	22153	22167	15
  	484	22265	22278	14
  	485	23110	23123	14
  	486	23114	23133	20
  	487	23286	23303	18
  	488	23364	23379	16
  	489	23478	23498	21
  	490	23544	23587	44
  	491	23589	23630	42
  	492	23658	23676	19
  	493	23678	23702	25
  	494	23704	23729	26
  	495	23731	23748	18
  	496	23740	23755	16
  	497	23744	23757	14
  	498	23750	23764	15
  	499	23767	23795	29
  	500	23802	23816	15
  	501	23818	23831	14
  	502	23855	23869	15
  	503	23906	23926	21
  	504	23928	23942	15
  	505	23994	24007	14
  	506	24005	24018	14
  	507	24023	24056	34
  	508	24074	24088	15
  	509	24088	24104	17
  	510	24112	24163	52
  	511	24199	24212	14
  	512	24231	24244	14
  	513	24237	24252	16
  	514	24254	24267	14
  	515	24281	24325	45
  	516	24327	24353	27
  	517	24355	24374	20
  	518	24376	24399	24
  	519	24401	24416	16
  	520	24442	24489	48
  	521	24492	24506	15
  	522	24498	24511	14
  	523	24538	24556	19
  	524	24546	24562	17
  	525	24591	24618	28
  	526	24620	24633	14
  	527	24635	24650	16
  	528	24665	24681	17
  	529	24687	24706	20
  	530	24709	24729	21
  	531	24731	24752	22
  	532	24756	24771	16
  	533	24773	24788	16
  	534	24793	24821	29
  	535	24823	24854	32
  	536	24856	24870	15
  	537	24873	24922	50
  	538	24933	24954	22
  	539	24965	24984	20
  	540	25019	25052	34
  	541	25054	25099	46
  	542	25112	25125	14
  	543	25133	25169	37
  	544	25171	25184	14
  	545	25186	25221	36
  	546	25236	25253	18
  	547	25246	25296	51
  	548	25298	25336	39
  	549	25332	25348	17
  	550	25349	25363	15
  	551	25388	25432	45
  	552	25439	25462	24
  	553	25509	25523	15
  	554	25525	25547	23
  	555	25578	25593	16
  	556	25587	25601	15
  	557	25604	25617	14
  	558	25633	25655	23
  	559	25672	25716	45
  	560	25725	25738	14
  	561	25764	25800	37
  	562	25802	25828	27
  	563	25831	25846	16
  	564	25851	25872	22
  	565	25877	25904	28
  	566	25921	25946	26
  	567	25943	25970	28
  	568	25972	25986	15
  	569	26051	26064	14
  	570	26068	26086	19
  	571	26113	26137	25
  	572	26139	26159	21
  	573	26182	26197	16
  	574	26243	26296	54
  	575	26298	26313	16
  	576	26327	26350	24
  	577	26366	26385	20
  	578	26387	26404	18
  	579	26397	26415	19
  	580	26416	26453	38
  	581	26447	26461	15
  	582	26457	26471	15
  	583	26481	26498	18
  	584	26502	26525	24
  	585	26528	26562	35
  	586	26564	26590	27
  	587	26590	26622	33
  	588	26624	26638	15
  	589	26687	26702	16
  	590	26706	26719	14
  	591	26717	26730	14
  	592	26729	26743	15
  	593	26767	26797	31
  	594	26796	26816	21
  	595	26831	26847	17
  	596	26837	26850	14
  	597	26877	26890	14
  	598	26900	26922	23
  	599	26911	26933	23
  	600	26933	26946	14
  	601	26938	26977	40
  	602	26979	26992	14
  	603	26981	27017	37
  	604	27023	27041	19
  	605	27039	27055	17
  	606	27075	27121	47
  	607	27138	27153	16
  	608	27163	27266	104
  	609	27270	27293	24
  	610	27325	27358	34
  	611	27363	27408	46
  	612	27419	27448	30
  	613	27450	27469	20
  	614	27471	27498	28
  	615	27510	27523	14
  	616	27535	27562	28
  	617	28098	28119	22
  	618	28136	28155	20
  	619	28169	28197	29
  	620	28199	28212	14
  	621	28221	28244	24
  	622	28271	28285	15
  	623	28400	28414	15
  	624	28441	28476	36
  	625	28490	28533	44
  	626	28535	28562	28
  	627	28575	28600	26
  	628	28621	28634	14
  	629	28650	28663	14
  	630	28674	28687	14
  	631	28681	28699	19
  	632	28713	28730	18
  	633	28736	28761	26
  	634	28763	28811	49
  	635	28821	28854	34
  	636	28856	28881	26
  	637	28883	28920	38
  	638	28922	28947	26
  	639	28979	29006	28
  	640	29008	29056	49
  	641	29078	29095	18
  	642	29098	29129	32
  	643	29122	29135	14
  	644	29131	29144	14
  	645	29144	29158	15
  	646	29160	29207	48
  	647	29209	29230	22
  	648	29234	29266	33
  	649	29268	29286	19
  	650	29301	29315	15
  	651	29304	29323	20
  	652	29330	29352	23
  	653	29344	29358	15
  	654	29347	29365	19
  	655	29377	29402	26
  	656	29402	29422	21
  	657	29424	29445	22
  	658	29443	29457	15
  	659	29447	29460	14
  	660	29462	29475	14
  	661	29491	29512	22
  	662	29514	29551	38
  	663	29547	29560	14
  	664	29553	29620	68
  	665	29625	29700	76
  	666	29714	29745	32
  	667	29774	29805	32
  	668	29816	29847	32
  	669	29875	29892	18
  	670	29894	29908	15
  	671	29897	29910	14
  	672	29917	29938	22
  	673	29939	29952	14
  	674	29961	29976	16
  	675	29974	29987	14
  	676	29978	30001	24
  	677	30006	30023	18
  	678	30025	30039	15
  	679	30043	30107	65
  	680	30145	30158	14
  	681	30149	30166	18
  	682	30173	30228	56
  	683	30230	30250	21
  	684	30251	30309	59
  	685	30321	30358	38
  	686	30359	30380	22
  	687	30382	30422	41
  	688	30428	30442	15
  	689	30455	30482	28
  	690	30484	30498	15
  	691	30516	30531	16
  	692	30533	30646	114
  	693	30654	30745	92
  	694	30745	30760	16
  	695	30752	30766	15
  	696	30788	30843	56
  	697	30845	30867	23
  	698	30869	30912	44
  	699	30906	30920	15
  	700	30934	30951	18
  	701	30962	30984	23
  	702	30989	31002	14
  	703	31010	31033	24
  	704	31036	31062	27
  	705	31092	31106	15
  	706	31128	31166	39
  	707	31168	31182	15
  	708	31189	31203	15
  	709	31205	31218	14
  	710	31224	31253	30
  	711	31256	31272	17
  	712	31274	31292	19
  	713	31294	31322	29
  	714	31324	31353	30
  	715	31357	31370	14
  	716	31373	31399	27
  	717	31403	31426	24
  	718	31445	31460	16
  	719	31463	31483	21
  	720	31485	31501	17
  	721	31494	31508	15
  	722	31507	31529	23
  	723	31531	31565	35
  	724	31567	31615	49
  	725	31630	31665	36
  	726	31675	31691	17
  	727	31703	31721	19
  	728	31729	31769	41
  	729	31770	31790	21
  	730	31795	31813	19
  	731	31815	31835	21
  	732	31837	31865	29
  	733	31876	31889	14
  	734	31920	31945	26
  	735	31962	31978	17
  	736	31983	32014	32
  	737	32029	32050	22
  	738	32058	32110	53
  	739	32129	32147	19
  	740	32166	32242	77
  	741	32244	32279	36
  	742	32296	32315	20
  	743	32334	32396	63
  	744	32398	32425	28
  	745	32427	32453	27
  	746	32459	32481	23
  	747	32475	32498	24
  	748	32490	32523	34
  	749	32519	32534	16
  	750	32525	32547	23
  	751	32542	32555	14
  	752	32559	32572	14
  	753	32574	32587	14
  	754	32595	32618	24
  	755	32613	32626	14
  	756	32627	32649	23
  	757	32651	32664	14
  	758	32655	32689	35
  	759	32693	32719	27
  	760	32721	32750	30
  	761	32752	32778	27
  	762	32780	32795	16
  	763	32797	32847	51
  	764	32881	32894	14
  	765	32891	32904	14
  	766	32896	32911	16
  	767	32927	32972	46
  	768	32986	33017	32
  	769	33019	33036	18
  	770	33038	33096	59
  	771	33102	33123	22
  	772	33132	33145	14
  	773	33150	33163	14
  	774	33166	33199	34
  	775	33214	33260	47
  	776	33262	33292	31
  	777	33294	33307	14
  	778	33316	33351	36
  	779	33360	33402	43
  	780	33412	33425	14
  	781	33427	33442	16
  	782	33439	33452	14
  	783	33443	33456	14
  	784	33460	33501	42
  	785	33503	33535	33
  	786	33542	33557	16
  	787	34168	34181	14
  	788	34370	34385	16
  	789	35422	35435	14
  	790	35627	35641	15
  	791	35685	35700	16
  	792	35837	35851	15
  	793	35849	35864	16
  	794	35866	35879	14
  	795	35974	35987	14
  	796	36009	36042	34
  	797	36044	36079	36
  	798	36081	36097	17
  	799	36099	36120	22
  	800	36119	36133	15
  	801	36147	36163	17
  	802	36171	36200	30
  	803	36216	36241	26
  	804	36245	36274	30
  	805	36265	36283	19
  	806	36295	36348	54
  	807	36352	36389	38
  	808	36383	36400	18
  	809	36402	36419	18
  	810	36475	36520	46
  	811	36522	36539	18
  	812	36541	36626	86
  	813	36652	36672	21
  	814	36675	36705	31
  	815	36707	36746	40
  	816	36780	36808	29
  	817	36810	36823	14
  	818	36825	36901	77
  	819	36903	36922	20
  	820	36924	36982	59
  	821	36999	37030	32
  	822	37056	37083	28
  	823	37091	37135	45
  	824	37194	37221	28
  	825	37238	37277	40
  	826	37280	37294	15
  	827	37298	37315	18
  	828	37325	37350	26
  	829	37363	37383	21
  	830	37377	37394	18
  	831	37384	37397	14
  	832	37390	37438	49
  	833	37456	37481	26
  	834	37478	37491	14
  	835	37481	37503	23
  	836	37506	37524	19
  	837	37526	37545	20
  	838	37540	37572	33
  	839	37574	37590	17
  	840	37601	37616	16
  	841	37621	37658	38
  	842	37673	37690	18
  	843	37703	37738	36
  	844	37740	37753	14
  	845	37764	37790	27
  	846	37800	37818	19
  	847	37820	37850	31
  	848	37888	37909	22
  	849	37911	37972	62
  	850	37986	38014	29
  	851	38016	38032	17
  	852	38034	38053	20
  	853	38055	38073	19
  	854	38075	38090	16
  	855	38092	38128	37
  	856	38141	38167	27
  	857	38171	38194	24
  	858	38213	38240	28
  	859	38264	38286	23
  	860	38288	38370	83
  	861	38394	38420	27
  	862	38452	38467	16
  	863	38471	38487	17
  	864	38477	38490	14
  	865	38494	38507	14
  	866	38536	38556	21
  	867	38580	38593	14
  	868	38602	38618	17
  	869	38628	38654	27
  	870	38693	38709	17
  	871	38709	38722	14
  	872	38711	38725	15
  	873	38740	38756	17
  	874	38749	38769	21
  	875	38772	38797	26
  	876	38827	38846	20
  	877	38860	38883	24
  	878	38885	38905	21
  	879	38911	38931	21
  	880	38933	38949	17
  	881	38962	39032	71
  	882	39034	39047	14
  	883	39049	39070	22
  	884	39075	39115	41
  	885	39127	39143	17
  	886	39148	39162	15
  	887	39164	39222	59
  	888	39218	39231	14
  	889	39224	39256	33
  	890	39265	39306	42
  	891	39297	39311	15
  	892	39308	39343	36
  	893	39345	39359	15
  	894	39361	39381	21
  	895	39370	39383	14
  	896	39383	39399	17
  	897	39417	39469	53
  	898	39490	39503	14
  	899	39500	39522	23
  	900	39535	39549	15
  	901	39551	39611	61
  	902	39628	39647	20
  	903	39649	39690	42
  	904	39707	39759	53
  	905	39773	39797	25
  	906	39799	39858	60
  	907	39872	39928	57
  	908	39930	39969	40
  	909	39973	39997	25
  	910	39998	40013	16
  	911	40015	40064	50
  	912	40067	40108	42
  	913	40110	40140	31
  	914	40147	40163	17
  	915	40154	40179	26
  	916	40181	40196	16
  	917	40232	40282	51
  	918	40284	40307	24
  	919	40309	40368	60
  	920	40381	40399	19
  	921	40431	40471	41
  	922	40479	40493	15
  	923	40484	40522	39
  	924	40524	40544	21
  	925	40547	40561	15
  	926	40577	40594	18
  	927	40586	40599	14
  	928	40616	40631	16
  	929	40634	40647	14
  	930	40674	40727	54
  	931	40738	40755	18
  	932	40749	40771	23
  	933	40780	40802	23
  	934	40811	40834	24
  	935	40847	40865	19
  	936	40861	40875	15
  	937	40869	40897	29
  	938	40899	40919	21
  	939	40921	40939	19
  	940	40942	40962	21
  	941	40967	40980	14
  	942	41008	41097	90
  	943	41099	41131	33
  	944	41133	41200	68
  	945	41202	41223	22
  	946	41225	41242	18
  	947	41266	41279	14
  	948	41275	41298	24
  	949	41300	41321	22
  	950	41325	41360	36
  	951	41367	41388	22
  	952	41403	41421	19
  	953	41439	41462	24
  	954	41481	41496	16
  	955	41508	41523	16
  	956	41531	41550	20
  	957	41552	41590	39
  	958	41590	41603	14
  	959	41612	41662	51
  	960	41664	41688	25
  	961	41685	41698	14
  	962	41691	41716	26
  	963	41718	41764	47
  	964	41761	41776	16
  	965	41778	41809	32
  	966	41798	41811	14
  	967	41838	41866	29
  	968	41872	41893	22
  	969	41885	41898	14
  	970	41912	41925	14
  	971	41914	41930	17
  	972	41923	41942	20
  	973	41933	41956	24
  	974	41962	41978	17
  	975	41997	42012	16
  	976	42026	42042	17
  	977	42035	42048	14
  	978	42037	42050	14
  	979	42048	42064	17
  	980	42056	42079	24
  	981	42081	42095	15
  	982	42096	42139	44
  	983	42141	42187	47
  	984	42190	42226	37
  	985	42232	42253	22
  	986	42255	42305	51
  	987	42307	42320	14
  	988	42347	42375	29
  	989	42389	42425	37
  	990	42427	42442	16
  	991	42452	42474	23
  	992	42482	42496	15
  	993	42495	42509	15
  	994	42536	42550	15
  	995	42566	42580	15
  	996	42590	42612	23
  	997	42646	42678	33
  	998	42683	42723	41
  	999	42735	42750	16
  	1000	42752	42817	66
  	1001	42843	42873	31
  	1002	42890	42939	50
  	1003	42938	42989	52
  	1004	42991	43005	15
  	1005	43007	43020	14
  	1006	43036	43055	20
  	1007	43057	43102	46
  	1008	43113	43145	33
  	1009	43147	43180	34
  	1010	43204	43221	18
  	1011	43221	43265	45
  	1012	43267	43296	30
  	1013	43311	43334	24
  	1014	43336	43361	26
  	1015	43371	43395	25
  	1016	43399	43423	25
  	1017	43425	43453	29
  	1018	43452	43468	17
  	1019	43470	43488	19
  	1020	43495	43522	28
  	1021	43525	43559	35
  	1022	43561	43584	24
  	1023	43590	43611	22
  	1024	43618	43650	33
  	1025	43670	43685	16
  	1026	43722	43774	53
  	1027	43776	43791	16
  	1028	43808	43835	28
  	1029	43835	43851	17
  	1030	43853	43868	16
  	1031	43923	43937	15
  	1032	43952	43987	36
  	1033	44011	44029	19
  	1034	44028	44070	43
  	1035	44072	44094	23
  	1036	44101	44130	30
  	1037	44137	44205	69
  	1038	44224	44244	21
  	1039	44246	44265	20
  	1040	44267	44318	52
  	1041	44316	44336	21
  	1042	44338	44359	22
  	1043	44361	44424	64
  	1044	44439	44474	36
  	1045	44476	44500	25
  	1046	44502	44519	18
  	1047	44539	44553	15
  	1048	44563	44578	16
  	1049	44585	44599	15
  	1050	44601	44617	17
  	1051	44640	44701	62
  	1052	44704	44723	20
  	1053	44741	44763	23
  	1054	44766	44846	81
  	1055	44870	44889	20
  	1056	44887	44905	19
  	1057	44920	44947	28
  	1058	44949	44966	18
  	1059	44994	45022	29
  	1060	45042	45059	18
  	1061	45061	45087	27
  	1062	45116	45154	39
  	1063	45156	45182	27
  	1064	45183	45198	16
  	1065	45210	45243	34
  	1066	45245	45320	76
  	1067	45331	45367	37
  	1068	45380	45399	20
  	1069	45415	45428	14
  	1070	45421	45486	66
  	1071	45488	45545	58
  	1072	45556	45576	21
  	1073	45578	45597	20
  	1074	45603	45650	48
  	1075	45652	45665	14
  	1076	45675	45715	41
  	1077	45749	45763	15
  	1078	45804	45826	23
  	1079	45839	45861	23
  	1080	45878	45910	33
  	1081	45926	45954	29
  	1082	45956	45975	20
  	1083	45977	45997	21
  	1084	45999	46020	22
  	1085	46046	46063	18
  	1086	46065	46088	24
  	1087	46097	46118	22
  	1088	46120	46142	23
  	1089	46144	46160	17
  	1090	46162	46185	24
  	1091	46204	46280	77
  	1092	46302	46326	25
  	1093	46328	46355	28
  	1094	46358	46377	20
  	1095	46379	46436	58
  	1096	46457	46471	15
  	1097	46473	46492	20
  	1098	46501	46541	41
  	1099	46543	46572	30
  	1100	46584	46626	43
  	1101	46655	46683	29
  	1102	46685	46702	18
  	1103	46704	46722	19
  	1104	46724	46763	40
  	1105	46784	46800	17
  	1106	46802	46827	26
  	1107	46830	46867	38
  	1108	46869	46887	19
  	1109	46889	46920	32
  	1110	46922	46947	26
  	1111	46976	47009	34
  	1112	47011	47030	20
  	1113	47032	47064	33
  	1114	47066	47092	27
  	1115	47108	47130	23
  	1116	47132	47168	37
  	1117	47170	47199	30
  	1118	47201	47222	22
  	1119	47238	47277	40
  	1120	47296	47350	55
  	1121	47352	47391	40
  	1122	47416	47440	25
  	1123	47452	47466	15
  	1124	47468	47523	56
  	1125	47522	47546	25
  	1126	47548	47567	20
  	1127	47569	47595	27
  	1128	47597	47634	38
  	1129	47657	47693	37
  	1130	47712	47731	20
  	1131	47749	47762	14
  	1132	47771	47825	55
  	1133	47827	47846	20
  	1134	47848	47872	25
  	1135	47874	47888	15
  	1136	47890	47909	20
  	1137	47911	47925	15
  	1138	47927	47952	26
  	1139	47961	47993	33
  	1140	48001	48016	16
  	1141	48051	48083	33
  	1142	48096	48158	63
  	1143	48158	48176	19
  	1144	48186	48201	16
  	1145	48213	48239	27
  	1146	48241	48256	16
  	1147	48258	48278	21
  	1148	48280	48339	60
  	1149	48341	48357	17
  	1150	48359	48377	19
  	1151	48379	48393	15
  	1152	48395	48488	94
  	1153	48492	48510	19
  	1154	48528	48549	22
  	1155	48550	48589	40
  	1156	48636	48658	23
  	1157	48683	48697	15
  	1158	48699	48762	64
  	1159	48762	48775	14
  	1160	48773	48832	60
  	1161	48873	48886	14
  	1162	48888	48914	27
  	1163	48916	48944	29
  	1164	48969	49008	40
  	1165	49010	49024	15
  	1166	49051	49110	60
  	1167	49116	49150	35
  	1168	49151	49184	34
  	1169	49187	49200	14
  	1170	49213	49230	18
  	1171	49233	49247	15
  	1172	49267	49284	18
  	1173	49297	49310	14
  	1174	49317	49369	53
  	1175	49371	49435	65
  	1176	49444	49458	15
  	1177	49467	49500	34
  	1178	49510	49538	29
  	1179	49540	49559	20
  	1180	49561	49584	24
  	1181	49591	49626	36
  	1182	49628	49646	19
  	1183	49653	49737	85
  	1184	49787	49802	16
  	1185	49817	49835	19
  	1186	49841	49860	20
  	1187	49862	49883	22
  	1188	49885	49905	21
  	1189	49921	49950	30
  	1190	49961	49979	19
  	1191	49995	50051	57
  	1192	50053	50071	19
  	1193	50073	50088	16
  	1194	50132	50158	27
  	1195	50167	50183	17
  	1196	50201	50226	26
  	1197	50226	50239	14
  	1198	50259	50313	55
  	1199	50323	50341	19
  	1200	50343	50396	54
  	1201	50390	50403	14
  	1202	50398	50448	51
  	1203	50451	50483	33
  	1204	50489	50507	19
  	1205	50526	50548	23
  	1206	50550	50569	20
  	1207	50575	50602	28
  	1208	50606	50621	16
  	1209	50617	50630	14
  	1210	50623	50641	19
  	1211	50634	50647	14
  	1212	50644	50663	20
  	1213	50665	50684	20
  	1214	50705	50730	26
  	1215	50732	50763	32
  	1216	50766	50799	34
  	1217	50797	50823	27
  	1218	50838	50864	27
  	1219	50870	50884	15
  	1220	50885	50911	27
  	1221	50924	50937	14
  	1222	50939	50974	36
  	1223	50980	51008	29
  	1224	51015	51030	16
  	1225	51034	51047	14
  	1226	51075	51089	15
  	1227	51109	51123	15
  	1228	51135	51172	38
  	1229	51189	51216	28
  	1230	51241	51260	20
  	1231	51273	51294	22
  	1232	51296	51312	17
  	1233	51337	51357	21
  	1234	51356	51381	26
  	1235	51393	51465	73
  	1236	51476	51494	19
  	1237	51496	51515	20
  	1238	51530	51544	15
  	1239	51546	51572	27
  	1240	51586	51600	15
  	1241	51602	51617	16
  	1242	51619	51677	59
  	1243	51679	51700	22
  	1244	51727	51741	15
  	1245	51743	51821	79
  	1246	51826	51859	34
  	1247	51884	51912	29
  	1248	51918	51936	19
  	1249	51947	51979	33
  	1250	52004	52017	14
  	1251	52023	52048	26
  	1252	52141	52167	27
  	1253	52169	52188	20
  	1254	52204	52225	22
  	1255	52246	52262	17
  	1256	52289	52306	18
  	1257	52321	52339	19
  	1258	52341	52360	20
  	1259	52360	52428	69
  	1260	52430	52504	75
  	1261	52506	52567	62
  	1262	52579	52594	16
  	1263	52591	52610	20
  	1264	52612	52642	31
  	1265	52644	52667	24
  	1266	52672	52686	15
  	1267	52688	52702	15
  	1268	52715	52753	39
  	1269	52770	52783	14
  	1270	52779	52792	14
  	1271	52814	52845	32
  	1272	52834	52857	24
  	1273	52858	52885	28
  	1274	52887	52943	57
  	1275	52945	52962	18
  	1276	52971	53019	49
  	1277	53011	53036	26
  	1278	53053	53066	14
  	1279	53092	53112	21
  	1280	53124	53151	28
  	1281	53161	53175	15
  	1282	53184	53220	37
  	1283	53222	53243	22
  	1284	53245	53260	16
  	1285	53278	53304	27
  	1286	53311	53346	36
  	1287	53364	53386	23
  	1288	53388	53404	17
  	1289	53417	53431	15
  	1290	53449	53463	15
  	1291	53465	53484	20
  	1292	53514	53527	14
  	1293	53552	53567	16
  	1294	53570	53591	22
  	1295	53618	53644	27
  	1296	53645	53667	23
  	1297	53669	53684	16
  	1298	53714	53742	29
  	1299	53744	53764	21
  	1300	53818	53843	26
  	1301	53845	53860	16
  	1302	53875	53889	15
  	1303	53961	53991	31
  	1304	53991	54013	23
  	1305	54015	54055	41
  	1306	54057	54081	25
  	1307	54114	54135	22
  	1308	54163	54178	16
  	1309	54180	54193	14
  	1310	54195	54254	60
  	1311	54261	54290	30
  	1312	54292	54307	16
  	1313	54309	54327	19
  	1314	54357	54372	16
  	1315	54404	54420	17
  	1316	54418	54439	22
  	1317	54441	54466	26
  	1318	54468	54512	45
  	1319	54519	54532	14
  	1320	54555	54572	18
  	1321	54588	54601	14
  	1322	54609	54633	25
  	1323	54644	54688	45
  	1324	54690	54721	32
  	1325	54723	54761	39
  	1326	54786	54802	17
  	1327	54819	54835	17
  	1328	54837	54912	76
  	1329	54924	54941	18
  	1330	54999	55017	19
  	1331	55019	55035	17
  	1332	55060	55073	14
  	1333	55075	55100	26
  	1334	55129	55171	43
  	1335	55173	55188	16
  	1336	55190	55203	14
  	1337	55210	55230	21
  	1338	55233	55281	49
  	1339	55276	55289	14
  	1340	55283	55320	38
  	1341	55330	55379	50
  	1342	55381	55423	43
  	1343	55420	55441	22
  	1344	55486	55502	17
  	1345	55515	55533	19
  	1346	55535	55553	19
  	1347	55555	55569	15
  	1348	55569	55588	20
  	1349	55590	55611	22
  	1350	55615	55663	49
  	1351	55665	55678	14
  	1352	55696	55713	18
  	1353	55715	55738	24
  	1354	55744	55774	31
  	1355	55776	55794	19
  	1356	55801	55823	23
  	1357	55862	55906	45
  	1358	55920	55933	14
  	1359	55922	55947	26
  	1360	55974	55993	20
  	1361	55990	56031	42
  	1362	56045	56073	29
  	1363	56082	56114	33
  	1364	56117	56140	24
  	1365	56183	56214	32
  	1366	56218	56236	19
  	1367	56261	56282	22
  	1368	56311	56336	26
  	1369	56331	56345	15
  	1370	56338	56358	21
  	1371	56369	56390	22
  	1372	56391	56431	41
  	1373	56433	56451	19
  	1374	56453	56473	21
  	1375	56475	56498	24
  	1376	56500	56546	47
  	1377	56558	56581	24
  	1378	56584	56597	14
  	1379	56611	56647	37
  	1380	56643	56657	15
  	1381	56667	56691	25
  	1382	56732	56759	28
  	1383	56788	56805	18
  	1384	56821	56845	25
  	1385	56850	56882	33
  	1386	56885	56906	22
  	1387	56928	56942	15
  	1388	56944	56959	16
  	1389	56961	56975	15
  	1390	56984	57002	19
  	1391	57004	57041	38
  	1392	57057	57082	26
  	1393	57084	57122	39
  	1394	57162	57222	61
  	1395	57224	57246	23
  	1396	57259	57284	26
  	1397	57317	57332	16
  	1398	57346	57369	24
  	1399	57388	57423	36
  	1400	57425	57440	16
  	1401	57442	57455	14
  	1402	57475	57492	18
  	1403	57508	57522	15
  	1404	57522	57546	25
  	1405	57548	57576	29
  	1406	57593	57634	42
  	1407	57658	57675	18
  	1408	57687	57771	85
  	1409	57786	57803	18
  	1410	57801	57819	19
  	1411	57830	57858	29
  	1412	57889	57911	23
  	1413	57926	57945	20
  	1414	57947	57972	26
  	1415	58009	58028	20
  	1416	58030	58060	31
  	1417	58063	58091	29
  	1418	58124	58146	23
  	1419	58147	58162	16
  	1420	58163	58198	36
  	1421	58214	58292	79
  	1422	58292	58309	18
  	1423	58336	58429	94
  	1424	58436	58457	22
  	1425	58453	58501	49
  	1426	58525	58553	29
  	1427	58566	58579	14
  	1428	58571	58584	14
  	1429	58586	58601	16
  	1430	58604	58630	27
  	1431	58656	58682	27
  	1432	58696	58713	18
  	1433	58722	58744	23
  	1434	58757	58771	15
  	1435	58805	58979	175
  	1436	58987	59073	87
  	1437	59072	59123	52
  	1438	59124	59150	27
  	1439	59154	59234	81
  	1440	59231	59276	46
  	1441	59291	59413	123
  	1442	59413	59458	46
  	1443	59466	59511	46
  	1444	59513	59533	21
  	1445	59549	59764	216
  	1446	59762	59825	64
  	1447	59824	59907	84
  	1448	59916	60004	89
  	1449	60006	60030	25
  	1450	60027	60040	14
  	1451	60032	60100	69
  	1452	60119	60188	70
  	1453	60191	60227	37
  	1454	60220	60287	68
  	1455	60289	60314	26
  	1456	60316	60554	239
  	1457	60556	60575	20
  	1458	60579	60593	15
  	1459	60595	60638	44
  	1460	60651	60690	40
  	1461	60692	60724	33
  	1462	60716	60799	84
  	1463	60801	60872	72
  	1464	60868	60881	14
  	1465	60885	60912	28
  	1466	60961	61009	49
  	1467	61014	61042	29
  	1468	61046	61059	14
  	1469	61053	61066	14
  	1470	61061	61084	24
  	1471	61134	61164	31
  	1472	61178	61199	22
  	1473	61201	61229	29
  	1474	61258	61284	27
  	1475	61286	61304	19
  	1476	61316	61332	17
  	1477	61341	61354	14
  	1478	61356	61383	28
  	1479	61407	61440	34
  	1480	61451	61468	18
  	1481	61470	61497	28
  	1482	61493	61506	14
  	1483	61499	61529	31
  	1484	61531	61558	28
  	1485	61590	61615	26
  	1486	61623	61640	18
  	1487	61673	61877	205
  	1488	61879	61898	20
  	1489	61900	61941	42
  	1490	61943	61962	20
  	1491	61964	61983	20
  	1492	62003	62017	15
  	1493	62015	62080	66
  	1494	62100	62124	25
  	1495	62133	62146	14
  	1496	62139	62175	37
  	1497	62191	62237	47
  	1498	62250	62270	21
  	1499	62283	62316	34
  	1500	62310	62358	49
  	1501	62357	62397	41
  	1502	62399	62413	15
  	1503	62415	62470	56
  	1504	62472	62501	30
  	1505	62503	62541	39
  	1506	62553	62609	57
  	1507	62611	62656	46
  	1508	62663	62690	28
  	1509	62703	62735	33
  	1510	62737	62759	23
  	1511	62765	62789	25
  	1512	62802	62816	15
  	1513	62810	62824	15
  	1514	62853	62868	16
  	1515	62864	62878	15
  	1516	62878	62907	30
  	1517	62905	62937	33
  	1518	62937	62951	15
  	1519	62943	62956	14
  	1520	62946	62960	15
  	1521	62961	62988	28
  	1522	62993	63006	14
  	1523	63005	63019	15
  	1524	63030	63049	20
  	1525	63057	63076	20
  	1526	63073	63088	16
  	1527	63078	63125	48
  	1528	63128	63152	25
  	1529	63154	63170	17
  	1530	63172	63196	25
  	1531	63185	63223	39
  	1532	63225	63245	21
  	1533	63236	63254	19
  	1534	63245	63261	17
  	1535	63263	63276	14
  	1536	63280	63295	16
  	1537	63292	63336	45
  	1538	63344	63368	25
  	1539	63369	63396	28
  	1540	63385	63398	14
  	1541	63395	63417	23
  	1542	63433	63451	19
  	1543	63440	63453	14
  	1544	63454	63470	17
  	1545	63472	63511	40
  	1546	63513	63539	27
  	1547	63547	63603	57
  	1548	63625	63651	27
  	1549	63676	63692	17
  	1550	63730	63746	17
  	1551	63759	63775	17
  	1552	63779	63833	55
  	1553	63844	63883	40
  	1554	63889	63907	19
  	1555	63910	63938	29
  	1556	63943	63962	20
  	1557	64004	64033	30
  	1558	64056	64087	32
  	1559	64112	64132	21
  	1560	64142	64158	17
  	1561	64160	64191	32
  	1562	64193	64209	17
  	1563	64214	64227	14
  	1564	64228	64241	14
  	1565	64254	64278	25
  	1566	64280	64298	19
  	1567	64300	64338	39
  	1568	64340	64355	16
  	1569	64357	64380	24
  	1570	64412	64434	23
  	1571	64438	64456	19
  	1572	64458	64488	31
  	1573	64490	64517	28
  	1574	64519	64538	20
  	1575	64552	64572	21
  	1576	64585	64608	24
  	1577	64625	64642	18
  	1578	64631	64644	14
  	1579	64644	64683	40
  	1580	64703	64716	14
  	1581	64736	64751	16
  	1582	64759	64773	15
  	1583	64775	64806	32
  	1584	64815	64831	17
  	1585	64845	64878	34
  	1586	64880	64904	25
  	1587	64915	64937	23
  	1588	64948	64971	24
  	1589	64973	64994	22
  	1590	64996	65017	22
  	1591	65019	65055	37
  	1592	65062	65109	48
  	1593	65111	65138	28
  	1594	65140	65179	40
  	1595	65181	65195	15
  	1596	65210	65230	21
  	1597	65232	65248	17
  	1598	65271	65296	26
  	1599	65298	65319	22
  	1600	65321	65371	51
  	1601	65391	65413	23
  	1602	65415	65436	22
  	1603	65436	65454	19
  	1604	65477	65490	14
  	1605	65492	65520	29
  	1606	65522	65552	31
  	1607	65554	65579	26
  	1608	65581	65594	14
  	1609	65591	65606	16
  	1610	65595	65616	22
  	1611	65618	65632	15
  	1612	65634	65657	24
  	1613	65661	65716	56
  	1614	65730	65747	18
  	1615	65748	65807	60
  	1616	65809	65829	21
  	1617	65831	65844	14
  	1618	65846	65859	14
  	1619	65861	65891	31
  	1620	65898	65920	23
  	1621	65930	65963	34
  	1622	65980	66060	81
  	1623	66069	66085	17
  	1624	66095	66108	14
  	1625	66110	66126	17
  	1626	66139	66173	35
  	1627	66175	66191	17
  	1628	66204	66226	23
  	1629	66224	66263	40
  	1630	66265	66278	14
  	1631	66280	66320	41
  	1632	66322	66345	24
  	1633	66355	66371	17
  	1634	66375	66407	33
  	1635	66411	66424	14
  	1636	66421	66441	21
  	1637	66440	66460	21
  	1638	66463	66482	20
  	1639	66484	66501	18
  	1640	66509	66527	19
  	1641	66534	66548	15
  	1642	66556	66569	14
  	1643	66562	66593	32
  	1644	66606	66637	32
  	1645	66639	66665	27
  	1646	66674	66690	17
  	1647	66692	66720	29
  	1648	66722	66742	21
  	1649	66758	66786	29
  	1650	66787	66802	16
  	1651	66812	66862	51
  	1652	66864	66885	22
  	1653	66940	66953	14
  	1654	66982	66997	16
  	1655	67024	67084	61
  	1656	67103	67118	16
  	1657	67156	67185	30
  	1658	67181	67195	15
  	1659	67193	67206	14
  	1660	67215	67229	15
  	1661	67231	67271	41
  	1662	67288	67301	14
  	1663	67294	67345	52
  	1664	67362	67379	18
  	1665	67381	67397	17
  	1666	67409	67448	40
  	1667	67468	67481	14
  	1668	67483	67510	28
  	1669	67540	67561	22
  	1670	67620	67640	21
  	1671	67656	67672	17
  	1672	67674	67749	76
  	1673	67751	67764	14
  	1674	67783	67801	19
  	1675	67803	67828	26
  	1676	67830	67848	19
  	1677	67850	67868	19
  	1678	67877	67918	42
  	1679	67933	67961	29
  	1680	67963	67978	16
  	1681	67998	68026	29
  	1682	68028	68046	19
  	1683	68048	68082	35
  	1684	68084	68112	29
  	1685	68114	68130	17
  	1686	68129	68155	27
  	1687	68170	68192	23
  	1688	68194	68237	44
  	1689	68239	68261	23
  	1690	68272	68286	15
  	1691	68290	68373	84
  	1692	68375	68419	45
  	1693	68442	68487	46
  	1694	68489	68547	59
  	1695	68549	68592	44
  	1696	68599	68614	16
  	1697	68617	68657	41
  	1698	68659	68686	28
  	1699	68688	68735	48
  	1700	68732	68747	16
  	1701	68749	68786	38
  	1702	68788	68830	43
  	1703	68837	68879	43
  	1704	68882	68899	18
  	1705	68918	68942	25
  	1706	68944	68968	25
  	1707	68983	69007	25
  	1708	69012	69027	16
  	1709	69020	69064	45
  	1710	69064	69077	14
  	1711	69079	69114	36
  	1712	69116	69196	81
  	1713	69185	69198	14
  	1714	69202	69219	18
  	1715	69228	69246	19
  	1716	69240	69282	43
  	1717	69294	69317	24
  	1718	69306	69324	19
  	1719	69333	69346	14
  	1720	69352	69366	15
  	1721	69387	69431	45
  	1722	69433	69447	15
  	1723	69452	69480	29
  	1724	69482	69497	16
  	1725	69491	69504	14
  	1726	69511	69564	54
  	1727	69566	69628	63
  	1728	69628	69642	15
  	1729	69659	69681	23
  	1730	69684	69697	14
  	1731	69719	69744	26
  	1732	69746	69763	18
  	1733	69765	69792	28
  	1734	69801	69828	28
  	1735	69853	69901	49
  	1736	69933	69949	17
  	1737	69951	69966	16
  	1738	69968	69983	16
  	1739	69988	70061	74
  	1740	70083	70100	18
  	1741	70110	70154	45
  	1742	70161	70199	39
  	1743	70202	70225	24
  	1744	70231	70246	16
  	1745	70269	70295	27
  	1746	70292	70327	36
  	1747	70331	70349	19
  	1748	70351	70371	21
  	1749	70381	70403	23
  	1750	70405	70420	16
  	1751	70422	70483	62
  	1752	70496	70533	38
  	1753	70535	70578	44
  	1754	70577	70639	63
  	1755	70653	70667	15
  	1756	70661	70674	14
  	1757	70669	70695	27
  	1758	70687	70705	19
  	1759	70708	70744	37
  	1760	70746	70764	19
  	1761	70766	70779	14
  	1762	70781	70832	52
  	1763	70834	70851	18
  	1764	70858	70887	30
  	1765	70889	70902	14
  	1766	70920	70933	14
  	1767	70935	70964	30
  	1768	70974	70987	14
  	1769	71008	71028	21
  	1770	71030	71046	17
  	1771	71048	71073	26
  	1772	71075	71106	32
  	1773	71108	71133	26
  	1774	71137	71152	16
  	1775	71153	71170	18
  	1776	71179	71192	14
  	1777	71197	71224	28
  	1778	71235	71251	17
  	1779	71253	71311	59
  	1780	71310	71329	20
  	1781	71330	71364	35
  	1782	71366	71386	21
  	1783	71388	71410	23
  	1784	71412	71433	22
  	1785	71448	71472	25
  	1786	71475	71491	17
  	1787	71491	71553	63
  	1788	71555	71581	27
  	1789	71583	71624	42
  	1790	71634	71700	67
  	1791	71706	71725	20
  	1792	71732	71747	16
  	1793	71789	71804	16
  	1794	71810	71824	15
  	1795	71819	71834	16
  	1796	71839	71872	34
  	1797	71876	71889	14
  	1798	71886	71908	23
  	1799	71910	71924	15
  	1800	71985	71999	15
  	1801	72000	72021	22
  	1802	72023	72047	25
  	1803	72071	72158	88
  	1804	72165	72192	28
  	1805	72194	72234	41
  	1806	72236	72255	20
  	1807	72257	72281	25
  	1808	72283	72299	17
  	1809	72312	72329	18
  	1810	72323	72336	14
  	1811	72348	72395	48
  	1812	72398	72411	14
  	1813	72413	72455	43
  	1814	72470	72503	34
  	1815	72506	72541	36
  	1816	72545	72558	14
  	1817	72560	72586	27
  	1818	72583	72597	15
  	1819	72588	72602	15
  	1820	72611	72636	26
  	1821	72638	72688	51
  	1822	72696	72736	41
  	1823	72738	72761	24
  	1824	72774	72799	26
  	1825	72801	72886	86
  	1826	72888	72903	16
  	1827	72928	72958	31
  	1828	72962	72990	29
  	1829	73001	73014	14
  	1830	73017	73053	37
  	1831	73055	73078	24
  	1832	73077	73090	14
  	1833	73088	73121	34
  	1834	73124	73153	30
  	1835	73147	73172	26
  	1836	73164	73203	40
  	1837	73218	73257	40
  	1838	73260	73273	14
  	1839	73268	73281	14
  	1840	73278	73291	14
  	1841	73298	73313	16
  	1842	73451	73465	15
  	1843	73459	73472	14
  	1844	73512	73567	56
  	1845	73569	73611	43
  	1846	73614	73645	32
  	1847	73661	73713	53
  	1848	73712	73727	16
  	1849	73716	73731	16
  	1850	73735	73748	14
  	1851	73741	73760	20
  	1852	73764	73782	19
  	1853	73783	73801	19
  	1854	73795	73829	35
  	1855	73860	73873	14
  	1856	73885	73904	20
  	1857	73906	73919	14
  	1858	73916	73945	30
  	1859	73947	73961	15
  	1860	73978	74018	41
  	1861	74020	74046	27
  	1862	74061	74082	22
  	1863	74092	74158	67
  	1864	74160	74177	18
  	1865	74179	74209	31
  	1866	74216	74245	30
  	1867	74270	74287	18
  	1868	74289	74305	17
  	1869	74307	74368	62
  	1870	74369	74411	43
  	1871	74416	74461	46
  	1872	74463	74479	17
  	1873	74506	74541	36
  	1874	74543	74636	94
  	1875	74647	74704	58
  	1876	74745	74770	26
  	1877	74789	74813	25
  	1878	74815	74838	24
  	1879	74850	74877	28
  	1880	74891	74923	33
  	1881	74925	74940	16
  	1882	74952	74969	18
  	1883	74979	75001	23
  	1884	75037	75066	30
  	1885	75068	75088	21
  	1886	75097	75123	27
  	1887	75131	75149	19
  	1888	75152	75189	38
  	1889	75210	75252	43
  	1890	75254	75276	23
  	1891	75288	75310	23
  	1892	75338	75357	20
  	1893	75359	75372	14
  	1894	75376	75397	22
  	1895	75405	75432	28
  	1896	75440	75470	31
  	1897	75482	75501	20
  	1898	75503	75540	38
  	1899	75544	75560	17
  	1900	75562	75576	15
  	1901	75589	75610	22
  	1902	75633	75646	14
  	1903	75648	75679	32
  	1904	75691	75709	19
  	1905	75711	75724	14
  	1906	75740	75764	25
  	1907	75763	75776	14
  	1908	75767	75790	24
  	1909	75780	75794	15
  	1910	75792	75808	17
  	1911	75810	75829	20
  	1912	75831	75863	33
  	1913	75865	75880	16
  	1914	75882	75922	41
  	1915	75932	75998	67
  	1916	76000	76026	27
  	1917	76028	76045	18
  	1918	76046	76082	37
  	1919	76098	76413	316
  	1920	76420	76442	23
  	1921	76456	76477	22
  	1922	76484	76558	75
  	1923	76573	76592	20
  	1924	76608	76622	15
  	1925	76627	76663	37
  	1926	76665	76683	19
  	1927	76685	76698	14
  	1928	76702	76716	15
  	1929	76725	76744	20
  	1930	76745	76761	17
  	1931	76780	76796	17
  	1932	76798	76812	15
  	1933	76814	76832	19
  	1934	76834	76859	26
  	1935	76871	76934	64
  	1936	77012	77034	23
  	1937	77039	77055	17
  	1938	77081	77094	14
  	1939	77121	77184	64
  	1940	77186	77200	15
  	1941	77202	77225	24
  	1942	77227	77247	21
  	1943	77261	77317	57
  	1944	77327	77340	14
  	1945	77342	77366	25
  	1946	77377	77394	18
  	1947	77396	77439	44
  	1948	77453	77468	16
  	1949	77462	77593	132
  	1950	77586	77599	14
  	1951	77595	77641	47
  	1952	77643	77728	86
  	1953	77730	77768	39
  	1954	77778	77816	39
  	1955	77818	77835	18
  	1956	77837	77855	19
  	1957	77861	77876	16
  	1958	77882	77898	17
  	1959	77900	77924	25
  	1960	77923	77936	14
  	1961	77957	77970	14
  	1962	77962	77985	24
  	1963	77994	78022	29
  	1964	78024	78056	33
  	1965	78079	78128	50
  	1966	78132	78158	27
  	1967	78173	78213	41
  	1968	78224	78265	42
  	1969	78275	78332	58
  	1970	78334	78440	107
  	1971	78442	78489	48
  	1972	78491	78505	15
  	1973	78501	78514	14
  	1974	78507	78537	31
  	1975	78557	78570	14
  	1976	78562	78623	62
  	1977	78625	78665	41
  	1978	78668	78684	17
  	1979	78686	78759	74
  	1980	78761	78787	27
  	1981	78793	78814	22
  	1982	78816	78854	39
  	1983	78847	78860	14
  	1984	78874	78909	36
  	1985	78917	78944	28
  	1986	78956	78978	23
  	1987	78991	79008	18
  	1988	79003	79032	30
  	1989	79026	79040	15
  	1990	79044	79072	29
  	1991	79098	79158	61
  	1992	79162	79182	21
  	1993	79184	79228	45
  	1994	79221	79235	15
  	1995	79230	79262	33
  	1996	79287	79333	47
  	1997	79356	79392	37
  	1998	79441	79476	36
  	1999	79488	79522	35
  	2000	79522	79539	18
  	2001	79568	79583	16
  	2002	79574	79601	28
  	2003	79603	79618	16
  	2004	79617	79639	23
  	2005	79651	79683	33
  	2006	79685	79724	40
  	2007	79721	79736	16
  	2008	79727	79782	56
  	2009	79784	79812	29
  	2010	79809	79834	26
  	2011	79841	79861	21
  	2012	79873	79923	51
  	2013	79928	79948	21
  	2014	79950	79986	37
  	2015	79993	80019	27
  	2016	80019	80063	45
  	2017	80071	80088	18
  	2018	80114	80160	47
  	2019	80154	80183	30
  	2020	80185	80212	28
  	2021	80214	80232	19
  	2022	80240	80266	27
  	2023	80293	80312	20
  	2024	80344	80380	37
  	2025	80382	80420	39
  	2026	80410	80423	14
  	2027	80417	80438	22
  	2028	80440	80456	17
  	2029	80467	80499	33
  	2030	80501	80527	27
  	2031	80532	80561	30
  	2032	80563	80599	37
  	2033	80604	80692	89
  	2034	80702	80737	36
  	2035	80739	80795	57
  	2036	80796	80871	76
  	2037	80873	80891	19
  	2038	80925	80961	37
  	2039	80963	80992	30
  	2040	81009	81068	60
  	2041	81070	81150	81
  	2042	81156	81199	44
  	2043	81201	81225	25
  	2044	81237	81253	17
  	2045	81255	81271	17
  	2046	81292	81351	60
  	2047	81353	81371	19
  	2048	81392	81422	31
  	2049	81438	81483	46
  	2050	81485	81503	19
  	2051	81512	81526	15
  	2052	81532	81554	23
  	2053	81556	81593	38
  	2054	81606	81664	59
  	2055	81666	81698	33
  	2056	81701	81720	20
  	2057	81728	81776	49
  	2058	81781	81810	30
  	2059	81812	81847	36
  	2060	81849	81893	45
  	2061	81908	81934	27
  	2062	81943	81964	22
  	2063	81967	82034	68
  	2064	82036	82134	99
  	2065	82136	82154	19
  	2066	82176	82197	22
  	2067	82199	82250	52
  	2068	82252	82269	18
  	2069	82271	82293	23
  	2070	82300	82314	15
  	2071	82329	82343	15
  	2072	82344	82357	14
  	2073	82378	82407	30
  	2074	82406	82422	17
  	2075	82421	82443	23
  	2076	82446	82469	24
  	2077	82490	82507	18
  	2078	82502	82523	22
  	2079	82547	82576	30
  	2080	82590	82603	14
  	2081	82628	82647	20
  	2082	82650	82666	17
  	2083	82669	82683	15
  	2084	82685	82716	32
  	2085	82715	82736	22
  	2086	82760	82785	26
  	2087	82778	82791	14
  	2088	82780	82818	39
  	2089	82811	82825	15
  	2090	82821	82864	44
  	2091	82883	82915	33
  	2092	82919	82935	17
  	2093	82930	82946	17
  	2094	82937	82957	21
  	2095	82959	82972	14
  	2096	82974	83000	27
  	2097	83020	83036	17
  	2098	83038	83088	51
  	2099	83090	83115	26
  	2100	83120	83140	21
  	2101	83142	83155	14
  	2102	83160	83186	27
  	2103	83198	83215	18
  	2104	83227	83246	20
  	2105	83273	83339	67
  	2106	83341	83385	45
  	2107	83387	83400	14
  	2108	83413	83426	14
  	2109	83417	83449	33
  	2110	83486	83520	35
  	2111	83522	83565	44
  	2112	83567	83581	15
  	2113	83576	83670	95
  	2114	83681	83701	21
  	2115	83703	83716	14
  	2116	83733	83817	85
  	2117	83817	83830	14
  	2118	83832	83853	22
  	2119	83855	83871	17
  	2120	83886	83926	41
  	2121	83958	83974	17
  	2122	83976	83991	16
  	2123	83993	84031	39
  	2124	84033	84067	35
  	2125	84069	84102	34
  	2126	84104	84121	18
  	2127	84143	84233	91
  	2128	84249	84281	33
  	2129	84283	84403	121
  	2130	84404	84432	29
  	2131	84431	84444	14
  	2132	84434	84490	57
  	2133	84503	84520	18
  	2134	84522	84555	34
  	2135	84557	84572	16
  	2136	84574	84597	24
  	2137	84607	84626	20
  	2138	84650	84675	26
  	2139	84677	84700	24
  	2140	84721	84753	33
  	2141	84755	84807	53
  	2142	84809	84826	18
  	2143	84831	84849	19
  	2144	84879	84893	15
  	2145	84895	84915	21
  	2146	84917	84961	45
  	2147	85234	85247	14
  	2148	85253	85267	15
  	2149	85256	85351	96
  	2150	85359	85374	16
  	2151	85363	85376	14
  	2152	85365	85381	17
  	2153	85380	85414	35
  	2154	85416	85454	39
  	2155	85456	85484	29
  	2156	85509	85545	37
  	2157	85535	85550	16
  	2158	85566	85584	19
  	2159	85586	85610	25
  	2160	85604	85627	24
  	2161	85628	85665	38
  	2162	85698	85723	26
  	2163	85713	85728	16
  	2164	85722	85735	14
  	2165	85770	85785	16
  	2166	85800	85813	14
  	2167	85875	85888	14
  	2168	85950	85963	14
  	2169	86097	86125	29
  	2170	86127	86142	16
  	2171	86175	86198	24
  	2172	86226	86242	17
  	2173	86237	86302	66
  	2174	86308	86327	20
  	2175	86321	86334	14
  	2176	86329	86382	54
  	2177	86384	86400	17
  	2178	86403	86417	15
  	2179	86414	86437	24
  	2180	86439	86455	17
  	2181	86461	86478	18
  	2182	86473	86487	15
  	2183	86480	86517	38
  	2184	86517	86531	15
  	2185	86565	86583	19
  	2186	86600	86632	33
  	2187	86634	86651	18
  	2188	86653	86678	26
  	2189	86697	86756	60
  	2190	86782	86796	15
  	2191	86786	86809	24
  	2192	86811	86855	45
  	2193	86857	86891	35
  	2194	86894	86908	15
  	2195	86916	86933	18
  	2196	86945	86959	15
  	2197	86951	86965	15
  	2198	86969	86990	22
  	2199	87017	87057	41
  	2200	87059	87073	15
  	2201	87062	87076	15
  	2202	87066	87089	24
  	2203	87097	87121	25
  	2204	87110	87134	25
  	2205	87130	87155	26
  	2206	87160	87194	35
  	2207	87185	87198	14
  	2208	87209	87260	52
  	2209	87257	87270	14
  	2210	87274	87287	14
  	2211	87276	87294	19
  	2212	87294	87328	35
  	2213	87317	87333	17
  	2214	87336	87360	25
  	2215	87368	87418	51
  	2216	87441	87460	20
  	2217	87462	87487	26
  	2218	87489	87518	30
  	2219	87520	87539	20
  	2220	87542	87570	29
  	2221	87572	87601	30
  	2222	87603	87644	42
  	2223	87642	87750	109
  	2224	87756	87776	21
  	2225	87778	87803	26
  	2226	87803	87837	35
  	2227	87872	87888	17
  	2228	87890	87917	28
  	2229	87949	87964	16
  	2230	87963	88008	46
  	2231	88010	88027	18
  	2232	88029	88046	18
  	2233	88048	88089	42
  	2234	88091	88108	18
  	2235	88110	88177	68
  	2236	88179	88192	14
  	2237	88194	88229	36
  	2238	88234	88259	26
  	2239	88261	88291	31
  	2240	88303	88328	26
  	2241	88328	88341	14
  	2242	88340	88354	15
  	2243	88356	88372	17
  	2244	88411	88446	36
  	2245	88448	88465	18
  	2246	88469	88511	43
  	2247	88518	88533	16
  	2248	88531	88557	27
  	2249	88547	88560	14
  	2250	88573	88593	21
  	2251	88597	88618	22
  	2252	88620	88690	71
  	2253	88692	88745	54
  	2254	88954	88973	20
  	2255	88988	89047	60
  	2256	89066	89091	26
  	2257	89098	89119	22
  	2258	89135	89149	15
  	2259	89151	89181	31
  	2260	89177	89193	17
  	2261	89223	89273	51
  	2262	89285	89300	16
  	2263	89315	89383	69
  	2264	89404	89442	39
  	2265	89444	89541	98
  	2266	89579	89639	61
  	2267	89660	89692	33
  	2268	89694	89741	48
  	2269	89773	89787	15
  	2270	89789	89817	29
  	2271	89826	89888	63
  	2272	89904	89922	19
  	2273	89937	89950	14
  	2274	89945	89958	14
  	2275	89956	89974	19
  	2276	89971	89985	15
  	2277	89979	89992	14
  	2278	89984	90000	17
  	2279	89999	90014	16
  	2280	90017	90041	25
  	2281	90036	90049	14
  	2282	90077	90093	17
  	2283	90099	90128	30
  	2284	90130	90155	26
  	2285	90157	90200	44
  	2286	90225	90256	32
  	2287	90258	90293	36
  	2288	90305	90318	14
  	2289	90320	90352	33
  	2290	90356	90370	15
  	2291	90400	90421	22
  	2292	90423	90461	39
  	2293	90464	90507	44
  	2294	90509	90530	22
  	2295	90529	90542	14
  	2296	90531	90567	37
  	2297	90569	90612	44
  	2298	90614	90730	117
  	2299	90732	90758	27
  	2300	90760	90885	126
  	2301	90887	90918	32
  	2302	90920	90946	27
  	2303	90938	90955	18
  	2304	90960	90973	14
  	2305	90965	90981	17
  	2306	90973	91000	28
  	2307	90997	91011	15
  	2308	91002	91019	18
  	2309	91059	91140	82
  	2310	91142	91157	16
  	2311	91157	91194	38
  	2312	91196	91231	36
  	2313	91233	91251	19
  	2314	91253	91274	22
  	2315	91296	91310	15
  	2316	91335	91367	33
  	2317	91406	91442	37
  	2318	91447	91477	31
  	2319	91489	91509	21
  	2320	91520	91621	102
  	2321	91623	91674	52
  	2322	91680	91703	24
  	2323	91715	91731	17
  	2324	91733	91771	39
  	2325	91773	91788	16
  	2326	91790	91805	16
  	2327	91807	91823	17
  	2328	91825	91859	35
  	2329	91861	91900	40
  	2330	91907	91926	20
  	2331	91928	91943	16
  	2332	91950	91980	31
  	2333	91982	91996	15
  	2334	91998	92011	14
  	2335	92010	92027	18
  	2336	92027	92067	41
  	2337	92069	92126	58
  	2338	92128	92321	194
  	2339	92323	92540	218
  	2340	92542	92558	17
  	2341	92566	92684	119
  	2342	92686	92726	41
  	2343	92728	92837	110
  	2344	92839	93032	194
  	2345	93034	93094	61
  	2346	93100	93209	110
  	2347	93211	93254	44
  	2348	93256	93323	68
  	2349	93325	93448	124
  	2350	93459	93477	19
  	2351	93475	93497	23
  	2352	93509	93530	22
  	2353	93532	93566	35
  	2354	93568	93601	34
  	2355	93606	93646	41
  	2356	93668	93716	49
  	2357	93718	93742	25
  	2358	93744	93788	45
  	2359	93790	93808	19
  	2360	93811	93832	22
  	2361	93874	93901	28
  	2362	93904	93986	83
  	2363	94021	94036	16
  	2364	94038	94079	42
  	2365	94073	94086	14
  	2366	94097	94116	20
  	2367	94118	94141	24
  	2368	94140	94219	80
  	2369	94242	94257	16
  	2370	94264	94335	72
  	2371	94337	94356	20
  	2372	94358	94378	21
  	2373	94373	94386	14
  	2374	94384	94403	20
  	2375	94405	94422	18
  	2376	94453	94497	45
  	2377	94497	94558	62
  	2378	94560	94605	46
  	2379	94630	94724	95
  	2380	94739	94752	14
  	2381	94755	94786	32
  	2382	94800	94815	16
  	2383	94872	94901	30
  	2384	94903	94953	51
  	2385	94955	95060	106
  	2386	95070	95085	16
  	2387	95093	95110	18
  	2388	95135	95149	15
  	2389	95154	95168	15
  	2390	95170	95210	41
  	2391	95227	95257	31
  	2392	95302	95318	17
  	2393	95311	95356	46
  	2394	95359	95401	43
  	2395	95403	95453	51
  	2396	95450	95463	14
  	2397	95475	95491	17
  	2398	95503	95553	51
  	2399	95555	95569	15
  	2400	95583	95609	27
  	2401	95634	95668	35
  	2402	95718	95738	21
  	2403	95727	95740	14
  	2404	95836	95849	14
  	2405	95851	95872	22
  	2406	95874	95888	15
  	2407	95890	95910	21
  	2408	95912	95925	14
  	2409	95938	95969	32
  	2410	95973	95990	18
  	2411	95992	96066	75
  	2412	96073	96087	15
  	2413	96103	96120	18
  	2414	96122	96167	46
  	2415	96169	96182	14
  	2416	96183	96211	29
  	2417	96213	96234	22
  	2418	96246	96279	34
  	2419	96300	96334	35
  	2420	96358	96375	18
  	2421	96377	96398	22
  	2422	96424	96467	44
  	2423	96496	96518	23
  	2424	96520	96535	16
  	2425	96540	96566	27
  	2426	96572	96592	21
  	2427	96604	96646	43
  	2428	96642	96655	14
  	2429	96648	96667	20
  	2430	96681	96728	48
  	2431	96730	96781	52
  	2432	96804	96829	26
  	2433	96831	96879	49
  	2434	96887	96916	17
  	2435	96928	96944	30
  	2436	96946	96959	14
  	2437	96970	96990	21
  	2438	96992	97021	30
  	2439	97023	97037	15
  	2440	97039	97073	35
  	2441	97075	97366	292
  	2442	97368	97393	26
  	2443	97420	97466	47
  	2444	97469	97507	39
  	2445	97513	97529	17
  	2446	97531	97583	53
  	2447	97585	97600	16
  	2448	97602	97631	30
  	2449	97633	97683	51
  	2450	97685	97703	19
  	2451	97705	97742	38
  	2452	97787	97803	17
  	2453	97805	97822	18
  	2454	97824	97876	53
  	2455	97878	97921	44
  	2456	97923	97943	21
  	2457	97945	97963	19
  	2458	97965	97994	30
  	2459	97995	98011	17
  	2460	98014	98044	31
  	2461	98039	98061	23
  	2462	98055	98076	22
  	2463	98077	98090	14
  	2464	98079	98092	14
  	2465	98085	98098	14
  	2466	98100	98115	16
  	2467	98113	98145	33
  	2468	98142	98160	19
  	2469	98162	98180	19
  	2470	98188	98219	32
  	2471	98215	98237	23
  	2472	98227	98240	14
  	2473	98232	98255	24
  	2474	98255	98268	14
  	2475	98264	98287	24
  	2476	98292	98326	35
  	2477	98373	98397	25
  	2478	98399	98428	30
  	2479	98442	98461	20
  	2480	98480	98501	22
  	2481	98499	98520	22
  	2482	98524	98538	15
  	2483	98537	98550	14
  	2484	98545	98585	41
  	2485	98595	98610	16
  	2486	98599	98624	26
  	2487	98644	98668	25
  	2488	98678	98704	27
  	2489	98703	98718	16
  	2490	98736	98754	19
  	2491	98778	98794	17
  	2492	98802	98821	20
  	2493	98845	98876	32
  	2494	98878	98900	23
  	2495	98900	98972	73
  	2496	98961	98976	16
  	2497	98974	98998	25
  	2498	99011	99029	19
  	2499	99033	99065	33
  	2500	99067	99107	41
  	2501	99151	99186	36
  	2502	99188	99219	32
  	2503	99222	99245	24
  	2504	99254	99276	23
  	2505	99288	99312	25
  	2506	99314	99338	25
  	2507	99367	99430	64
  	2508	99444	99491	48
  	2509	99496	99554	59
  	2510	99570	99585	16
  	2511	99587	99618	32
  	2512	99620	99669	50
  	2513	99679	99710	32
  	2514	99720	99748	29
  	2515	99750	99763	14
  	2516	99768	99805	38
  	2517	99818	99841	24
  	2518	99855	99879	25
  	2519	99881	99900	20
  	2520	99902	99932	31
  	2521	99934	99954	21
  	2522	99959	100011	53
  	2523	100011	100037	27
  	2524	100057	100071	15
  	2525	100073	100102	30
  	2526	100104	100118	15
  	2527	100131	100186	56
  	2528	100188	100201	14
  	2529	100194	100212	19
  	2530	100214	100277	64
  	2531	100279	100303	25
  	2532	100309	100355	47
  	2533	100349	100386	38
  	2534	100379	100393	15
  	2535	100388	100401	14
  	2536	100403	100423	21
  	2537	100452	100473	22
  	2538	100508	100542	35
  	2539	100548	100580	33
  	2540	100582	100612	31
  	2541	100614	100652	39
  	2542	100695	100714	20
  	2543	100736	100749	14
  	2544	100751	100790	40
  	2545	100808	100842	35
  	2546	100844	100860	17
  	2547	100862	100930	69
  	2548	100939	100953	15
  	2549	100955	100971	17
  	2550	100973	101003	31
  	2551	101021	101048	28
  	2552	101057	101093	37
  	2553	101109	101148	40
  	2554	101145	101189	45
  	2555	101194	101208	15
  	2556	101210	101244	35
  	2557	101256	101271	16
  	2558	101277	101300	24
  	2559	101310	101327	18
  	2560	101329	101345	17
  	2561	101374	101397	24
  	2562	101409	101426	18
  	2563	101453	101466	14
  	2564	101474	101487	14
  	2565	101481	101515	35
  	2566	101518	101541	24
  	2567	101542	101560	19
  	2568	101554	101591	38
  	2569	101593	101609	17
  	2570	101635	101695	61
  	2571	101707	101746	40
  	2572	101748	101763	16
  	2573	101774	101810	37
  	2574	101812	101828	17
  	2575	101819	101835	17
  	2576	101829	101842	14
  	2577	101842	101855	14
  	2578	101857	101878	22
  	2579	101880	101943	64
  	2580	101947	101981	35
  	2581	101988	102009	22
  	2582	102022	102066	45
  	2583	102068	102084	17
  	2584	102100	102113	14
  	2585	102115	102130	16
  	2586	102132	102145	14
  	2587	102192	102241	50
  	2588	102269	102285	17
  	2589	102312	102327	16
  	2590	102357	102392	36
  	2591	102407	102428	22
  	2592	102430	102444	15
  	2593	102460	102485	26
  	2594	102487	102508	22
  	2595	102532	102573	42
  	2596	102595	102642	48
  	2597	102653	102694	42
  	2598	102701	102718	18
  	2599	102720	102734	15
  	2600	102736	102757	22
  	2601	102799	102836	38
  	2602	102847	102882	36
  	2603	102890	102927	38
  	2604	102938	102971	34
  	2605	102982	103019	38
  	2606	103014	103027	14
  	2607	103027	103054	28
  	2608	103065	103088	24
  	2609	103090	103108	19
  	2610	103098	103112	15
  	2611	103117	103138	22
  	2612	103152	103170	19
  	2613	103174	103204	31
  	2614	103206	103234	29
  	2615	103240	103268	29
  	2616	103286	103325	40
  	2617	103327	103347	21
  	2618	103349	103384	36
  	2619	103386	103405	20
  	2620	103422	103449	28
  	2621	103451	103493	43
  	2622	103495	103509	15
  	2623	103511	103560	50
  	2624	103565	103582	18
  	2625	103585	103607	23
  	2626	103631	103645	15
  	2627	103653	103684	32
  	2628	103683	103696	14
  	2629	103691	103733	43
  	2630	103738	103762	25
  	2631	103752	103765	14
  	2632	103755	103768	14
  	2633	103758	103771	14
  	2634	103790	103814	25
  	2635	103803	103816	14
  	2636	103830	103865	36
  	2637	103900	103923	24
  	2638	103912	103933	22
  	2639	103945	103964	20
  	2640	103990	104005	16
  	2641	104024	104055	32
  	2642	104058	104077	20
  	2643	104086	104099	14
  	2644	104095	104122	28
  	2645	104124	104146	23
  	2646	104148	104168	21
  	2647	104162	104176	15
  	2648	104173	104187	15
  	2649	104201	104241	41
  	2650	104234	104266	33
  	2651	104268	104286	19
  	2652	104288	104302	15
  	2653	104304	104335	32
  	2654	104340	104354	15
  	2655	104356	104373	18
  	2656	104375	104391	17
  	2657	104393	104417	25
  	2658	104426	104439	14
  	2659	104448	104478	31
  	2660	104480	104504	25
  	2661	104519	104546	28
  	2662	104549	104580	32
  	2663	104604	104620	17
  	2664	104620	104646	27
  	2665	104654	104673	20
  	2666	104675	104691	17
  	2667	104689	104776	88
  	2668	104829	104842	14
  	2669	104838	104852	15
  	2670	104934	104952	19
  	2671	104956	104987	32
  	2672	104993	105045	53
  	2673	105041	105055	15
  	2674	105047	105078	32
  	2675	105090	105107	18
  	2676	105101	105115	15
  	2677	105109	105137	29
  	2678	105149	105167	19
  	2679	105163	105176	14
  	2680	105185	105237	53
  	2681	105230	105243	14
  	2682	105233	105250	18
  	2683	105260	105286	27
  	2684	105288	105340	53
  	2685	105345	105370	26
  	2686	105372	105402	31
  	2687	105441	105458	18
  	2688	105460	105521	62
  	2689	105526	105541	16
  	2690	105543	105560	18
  	2691	105562	105575	14
  	2692	105582	105606	25
  	2693	105616	105671	56
  	2694	105677	105704	28
  	2695	105703	105725	23
  	2696	105746	105759	14
  	2697	105750	105765	16
  	2698	105776	105796	21
  	2699	105798	105824	27
  	2700	105827	105907	81
  	2701	105924	105939	16
  	2702	105941	105963	23
  	2703	105990	106014	25
  	2704	106017	106048	32
  	2705	106039	106072	34
  	2706	106061	106074	14
  	2707	106073	106102	30
  	2708	106092	106107	16
  	2709	106114	106159	46
  	2710	106161	106180	20
  	2711	106197	106243	47
  	2712	106237	106250	14
  	2713	106243	106256	14
  	2714	106247	106267	21
  	2715	106273	106333	61
  	2716	106335	106367	33
  	2717	106369	106417	49
  	2718	106419	106471	53
  	2719	106486	106523	38
  	2720	106525	106538	14
  	2721	106552	106572	21
  	2722	106584	106598	15
  	2723	106609	106696	88
  	2724	106698	106723	26
  	2725	106725	106740	16
  	2726	106743	106781	39
  	2727	106783	106811	29
  	2728	106826	106866	41
  	2729	106875	106902	28
  	2730	106916	106935	20
  	2731	106942	106960	19
  	2732	106991	107010	20
  	2733	107019	107038	20
  	2734	107040	107072	33
  	2735	107079	107094	16
  	2736	107087	107101	15
  	2737	107090	107109	20
  	2738	107113	107127	15
  	2739	107129	107143	15
  	2740	107154	107172	19
  	2741	107174	107198	25
  	2742	107210	107226	17
  	2743	107226	107239	14
  	2744	107237	107274	38
  	2745	107296	107356	61
  	2746	107358	107381	24
  	2747	107383	107415	33
  	2748	107417	107433	17
  	2749	107435	107455	21
  	2750	107457	107508	52
  	2751	107510	107525	16
  	2752	107527	107546	20
  	2753	107559	107573	15
  	2754	107586	107617	32
  	2755	107643	107689	47
  	2756	107694	107716	23
  	2757	107744	107792	49
  	2758	107790	107832	43
  	2759	107834	107860	27
  	2760	107864	107896	33
  	2761	107898	107912	15
  	2762	107914	107953	40
  	2763	107967	107992	26
  	2764	107994	108008	15
  	2765	108010	108038	29
  	2766	108065	108084	20
  	2767	108113	108215	103
  	2768	108220	108249	30
  	2769	108253	108281	29
  	2770	108283	108304	22
  	2771	108317	108359	43
  	2772	108361	108375	15
  	2773	108386	108402	17
  	2774	108421	108440	20
  	2775	108538	108551	14
  	2776	108561	108575	15
  	2777	108577	108616	40
  	2778	108618	108665	48
  	2779	108677	108707	31
  	2780	108735	108768	34
  	2781	108762	108777	16
  	2782	108780	108824	45
  	2783	108842	108885	44
  	2784	108907	108970	64
  	2785	108983	109019	37
  	2786	109021	109053	33
  	2787	109055	109068	14
  	2788	109070	109099	30
  	2789	109097	109122	26
  	2790	109113	109132	20
  	2791	109125	109165	41
  	2792	109167	109181	15
  	2793	109183	109200	18
  	2794	109214	109248	35
  	2795	109256	109277	22
  	2796	109281	109298	18
  	2797	109298	109311	14
  	2798	109300	109318	19
  	2799	109324	109374	51
  	2800	109377	109397	21
  	2801	109399	109437	39
  	2802	109446	109461	16
  	2803	109463	109476	14
  	2804	109472	109485	14
  	2805	109478	109514	37
  	2806	109516	109540	25
  	2807	109556	109588	33
  	2808	109601	109644	44
  	2809	109661	109681	21
  	2810	109683	109709	27
  	2811	109707	109737	31
  	2812	109739	109754	16
  	2813	109754	109768	15
  	2814	109770	109798	29
  	2815	109810	109829	20
  	2816	109859	109877	19
  	2817	109879	109934	56
  	2818	109955	109975	21
  	2819	109975	109988	14
  	2820	109994	110096	103
  	2821	110103	110129	27
  	2822	110131	110152	22
  	2823	110153	110173	21
  	2824	110175	110195	21
  	2825	110192	110226	35
  	2826	110297	110312	16
  	2827	110301	110314	14
  	2828	110308	110333	26
  	2829	110335	110351	17
  	2830	110353	110368	16
  	2831	110376	110401	26
  	2832	110418	110462	45
  	2833	110464	110481	18
  	2834	110531	110558	28
  	2835	110571	110590	20
  	2836	110599	110639	41
  	2837	110630	110643	14
  	2838	110641	110661	21
  	2839	110668	110681	14
  	2840	110683	110709	27
  	2841	110717	110798	82
  	2842	110804	110849	46
  	2843	110853	110890	38
  	2844	110928	110966	39
  	2845	110971	111003	33
  	2846	111000	111013	14
  	2847	111015	111033	19
  	2848	111035	111050	16
  	2849	111062	111094	33
  	2850	111092	111105	14
  	2851	111107	111140	34
  	2852	111161	111203	43
  	2853	111209	111223	15
  	2854	111224	111280	57
  	2855	111275	111290	16
  	2856	111283	111303	21
  	2857	111305	111320	16
  	2858	111311	111347	37
  	2859	111355	111368	14
  	2860	111357	111371	15
  	2861	111360	111381	22
  	2862	111373	111421	49
  	2863	111412	111426	15
  	2864	111451	111468	18
  	2865	111467	111480	14
  	2866	111482	111496	15
  	2867	111486	111500	15
  	2868	111497	111510	14
  	2869	111531	111564	34
  	2870	111580	111606	27
  	2871	111616	111637	22
  	2872	111658	111671	14
  	2873	111674	111688	15
  	2874	111692	111710	19
  	2875	111712	111725	14
  	2876	111727	111761	35
  	2877	111781	111804	24
  	2878	111811	111828	18
  	2879	111831	111849	19
  	2880	111856	111871	16
  	2881	111901	111917	17
  	2882	111919	111940	22
  	2883	111942	111987	46
  	2884	111984	112002	19
  	2885	112004	112069	66
  	2886	112070	112091	22
  	2887	112093	112116	24
  	2888	112118	112132	15
  	2889	112139	112170	32
  	2890	112180	112196	17
  	2891	112204	112223	20
  	2892	112236	112283	48
  	2893	112329	112343	15
  	2894	112345	112383	39
  	2895	112385	112401	17
  	2896	112404	112423	20
  	2897	112463	112477	15
  	2898	112485	112547	63
  	2899	112563	112581	19
  	2900	112583	112597	15
  	2901	112607	112638	32
  	2902	112640	112664	25
  	2903	112683	112721	39
  	2904	112730	112759	30
  	2905	112773	112811	39
  	2906	112811	112825	15
  	2907	112828	112862	35
  	2908	112882	112912	31
  	2909	112914	112967	54
  	2910	112968	112982	15
  	2911	112984	113016	33
  	2912	113044	113064	21
  	2913	113074	113097	24
  	2914	113111	113153	43
  	2915	113169	113194	26
  	2916	113198	113212	15
  	2917	113214	113230	17
  	2918	113232	113263	32
  	2919	113265	113284	20
  	2920	113306	113328	23
  	2921	113330	113355	26
  	2922	113357	113371	15
  	2923	113404	113422	19
  	2924	113421	113489	69
  	2925	113533	113559	27
  	2926	113561	113574	14
  	2927	113595	113616	22
  	2928	113648	113700	53
  	2929	113702	113739	38
  	2930	113762	113823	62
  	2931	113825	113960	136
  	2932	113962	114015	54
  	2933	114017	114048	32
  	2934	114045	114124	80
  	2935	114151	114170	20
  	2936	114182	114218	37
  	2937	114230	114270	41
  	2938	114272	114292	21
  	2939	114296	114339	44
  	2940	114354	114433	80
  	2941	114440	114457	18
  	2942	114459	114484	26
  	2943	114478	114536	59
  	2944	114538	114559	22
  	2945	114567	114592	26
  	2946	114594	114610	17
  	2947	114612	114652	41
  	2948	114681	114752	72
  	2949	114775	114805	31
  	2950	114803	114816	14
  	2951	114807	114821	15
  	2952	114823	114847	25
  	2953	114868	114912	45
  	2954	114947	114961	15
  	2955	114974	114997	24
  	2956	115001	115015	15
  	2957	115004	115017	14
  	2958	115019	115069	51
  	2959	115060	115073	14
  	2960	115072	115085	14
  	2961	115087	115100	14
  	2962	115102	115124	23
  	2963	115132	115151	20
  	2964	115154	115168	15
  	2965	115188	115208	21
  	2966	115219	115256	38
  	2967	115258	115283	26
  	2968	115285	115300	16
  	2969	115331	115353	23
  	2970	115355	115372	18
  	2971	115380	115397	18
  	2972	115399	115412	14
  	2973	115426	115475	50
  	2974	115496	115510	15
  	2975	115521	115545	25
  	2976	115555	115580	26
  	2977	115582	115600	19
  	2978	115602	115621	20
  	2979	115653	115677	25
  	2980	115692	115720	29
  	2981	115722	115738	17
  	2982	115769	115783	15
  	2983	115792	115808	17
  	2984	115819	115837	19
  	2985	115846	115878	33
  	2986	115888	115901	14
  	2987	115916	115932	17
  	2988	115943	115956	14
  	2989	115967	115993	27
  	2990	115996	116014	19
  	2991	116027	116045	19
  	2992	116105	116127	23
  	2993	116126	116139	14
  	2994	116141	116158	18
  	2995	116171	116186	16
  	2996	116194	116208	15
  	2997	116257	116279	23
  	2998	116318	116373	56
  	2999	116375	116437	63
  	3000	116439	116454	16
  	3001	116456	116496	41
  	3002	116500	116532	33
  	3003	116534	116554	21
  	3004	116556	116573	18
  	3005	116575	116592	18
  	3006	116596	116615	20
  	3007	116617	116650	34
  	3008	116650	116664	15
  	3009	116666	116694	29
  	3010	116775	116792	18
  	3011	116794	116811	18
  	3012	116813	116838	26
  	3013	116840	116872	33
  	3014	116890	116911	22
  	3015	116921	116948	28
  	3016	116952	116988	37
  	3017	116990	117006	17
  	3018	117008	117036	29
  	3019	117059	117133	75
  	3020	117187	117207	21
  	3021	117204	117217	14
  	3022	117209	117237	29
  	3023	117239	117252	14
  	3024	117255	117275	21
  	3025	117277	117300	24
  	3026	117337	117371	35
  	3027	117373	117416	44
  	3028	117418	117450	33
  	3029	117456	117507	52
  	3030	117518	117532	15
  	3031	117534	117590	57
  	3032	117582	117604	23
  	3033	117593	117617	25
  	3034	117621	117648	28
  	3035	117640	117662	23
  	3036	117664	117688	25
  	3037	117690	117711	22
  	3038	117728	117743	16
  	3039	117747	117781	35
  	3040	117784	117801	18
  	3041	117792	117822	31
  	3042	117824	117842	19
  	3043	117850	117869	20
  	3044	117890	117940	51
  	3045	117936	117968	33
  	3046	117970	117990	21
  	3047	117989	118034	46
  	3048	118034	118057	24
  	3049	118061	118083	23
  	3050	118086	118122	37
  	3051	118122	118182	61
  	3052	118172	118186	15
  	3053	118197	118211	15
  	3054	118216	118275	60
  	3055	118291	118316	26
  	3056	118318	118354	37
  	3057	118373	118388	16
  	3058	118391	118405	15
  	3059	118407	118423	17
  	3060	118425	118456	32
  	3061	118465	118492	28
  	3062	118498	118521	24
  	3063	118533	118551	19
  	3064	118553	118581	29
  	3065	118587	118617	31
  	3066	118620	118679	60
  	3067	118687	118716	30
  	3068	118731	118771	41
  	3069	118779	118805	27
  	3070	118816	118830	15
  	3071	118832	118895	64
  	3072	118910	119065	156
  	3073	119067	119081	15
  	3074	119095	119140	46
  	3075	119170	119205	36
  	3076	119210	119232	23
  	3077	119230	119246	17
  	3078	119236	119252	17
  	3079	119255	119274	20
  	3080	119271	119284	14
  	3081	119290	119307	18
  	3082	119320	119335	16
  	3083	119357	119463	107
  	3084	119465	119483	19
  	3085	119485	119535	51
  	3086	119550	119571	22
  	3087	119577	119608	32
  	3088	119610	119646	37
  	3089	119648	119688	41
  	3090	119713	119752	40
  	3091	119743	119784	42
  	3092	119786	119800	15
  	3093	119822	119836	15
  	3094	119830	119847	18
  	3095	119849	119900	52
  	3096	119912	119925	14
  	3097	119960	119982	23
  	3098	119984	120013	30
  	3099	120038	120054	17
  	3100	120057	120090	34
  	3101	120092	120134	43
  	3102	120138	120154	17
  	3103	120157	120189	33
  	3104	120187	120200	14
  	3105	120191	120211	21
  	3106	120225	120239	15
  	3107	120242	120267	26
  	3108	120271	120301	31
  	3109	120320	120340	21
  	3110	120363	120406	44
  	3111	120406	120421	16
  	3112	120414	120468	55
  	3113	120457	120470	14
  	3114	120487	120518	32
  	3115	120545	120563	19
  	3116	120567	120587	21
  	3117	120589	120625	37
  	3118	120619	120633	15
  	3119	120650	120663	14
  	3120	120676	120694	19
  	3121	120703	120717	15
  	3122	120721	120737	17
  	3123	120755	120812	58
  	3124	120816	120838	23
  	3125	120843	120871	29
  	3126	120873	120899	27
  	3127	120903	120922	20
  	3128	120933	120946	14
  	3129	120936	120981	46
  	3130	120983	121004	22
  	3131	121006	121021	16
  	3132	121023	121036	14
  	3133	121035	121061	27
  	3134	121063	121079	17
  	3135	121081	121097	17
  	3136	121105	121134	30
  	3137	121138	121156	19
  	3138	121155	121168	14
  	3139	121158	121174	17
  	3140	121166	121189	24
  	3141	121194	121208	15
  	3142	121201	121218	18
  	3143	121213	121237	25
  	3144	121246	121271	26
  	3145	121298	121314	17
  	3146	121311	121324	14
  	3147	121327	121351	25
  	3148	121359	121388	30
  	3149	121390	121419	30
  	3150	121446	121462	17
  	3151	121468	121487	20
  	3152	121499	121515	17
  	3153	121517	121543	27
  	3154	121545	121564	20
  	3155	121575	121597	23
  	3156	121599	121617	19
  	3157	121619	121662	44
  	3158	121664	121681	18
  	3159	121683	121700	18
  	3160	121702	121751	50
  	3161	121773	121788	16
  	3162	121790	121805	16
  	3163	121807	121834	28
  	3164	121836	121857	22
  	3165	121859	121874	16
  	3166	121877	121925	49
  	3167	121923	121936	14
  	3168	121928	121943	16
  	3169	121962	121976	15
  	3170	121978	121992	15
  	3171	122004	122028	25
  	3172	122030	122056	27
  	3173	122046	122059	14
  	3174	122052	122072	21
  	3175	122080	122095	16
  	3176	122099	122122	24
  	3177	122143	122163	21
  	3178	122169	122189	21
  	3179	122258	122274	17
  	3180	122289	122309	21
  	3181	122311	122346	36
  	3182	122357	122395	39
  	3183	122446	122468	23
  	3184	122471	122489	19
  	3185	122491	122512	22
  	3186	122526	122541	16
  	3187	122543	122557	15
  	3188	122579	122592	14
  	3189	122606	122653	48
  	3190	122663	122690	28
  	3191	122728	122742	15
  	3192	122757	122770	14
  	3193	122779	122840	62
  	3194	122842	122857	16
  	3195	122900	122923	24
  	3196	122933	122955	23
  	3197	122968	123042	75
  	3198	123055	123076	22
  	3199	123094	123108	15
  	3200	123114	123134	21
  	3201	123143	123160	18
  	3202	123162	123180	19
  	3203	123184	123198	15
  	3204	123200	123235	36
  	3205	123237	123321	85
  	3206	123314	123329	16
  	3207	123342	123360	19
  	3208	123356	123389	34
  	3209	123391	123410	20
  	3210	123412	123453	42
  	3211	123455	123485	31
  	3212	123488	123503	16
  	3213	123506	123524	19
  	3214	123526	123543	18
  	3215	123545	123578	34
  	3216	123598	123634	37
  	3217	123654	123683	30
  	3218	123685	123706	22
  	3219	123710	123774	65
  	3220	123803	123816	14
  	3221	123818	123831	14
  	3222	123896	123939	44
  	3223	123941	123974	34
  	3224	123976	124021	46
  	3225	124026	124040	15
  	3226	124042	124079	38
  	3227	124091	124109	19
  	3228	124158	124185	28
  	3229	124238	124274	37
  	3230	124319	124332	14
  	3231	124335	124373	39
  	3232	124394	124412	19
  	3233	124419	124445	27
  	3234	124450	124470	21
  	3235	124472	124493	22
  	3236	124499	124520	22
  	3237	124522	124561	40
  	3238	124564	124595	32
  	3239	124607	124649	43
  	3240	124662	124729	68
  	3241	124750	124767	18
  	3242	124769	124793	25
  	3243	124812	124828	17
  	3244	124853	124906	54
  	3245	124923	124948	26
  	3246	124958	124986	29
  	3247	125023	125042	20
  	3248	125032	125046	15
  	3249	125065	125083	19
  	3250	125073	125091	19
  	3251	125093	125107	15
  	3252	125132	125149	18
  	3253	125139	125154	16
  	3254	125151	125200	50
  	3255	125201	125274	74
  	3256	125314	125329	16
  	3257	125331	125370	40
  	3258	125372	125386	15
  	3259	125411	125431	21
  	3260	125433	125462	30
  	3261	125475	125562	88
  	3262	125564	125589	26
  	3263	125605	125639	35
  	3264	125641	125699	59
  	3265	125719	125732	14
  	3266	125737	125769	33
  	3267	125815	125829	15
  	3268	125834	125848	15
  	3269	125850	125884	35
  	3270	125899	125966	68
  	3271	125967	125999	33
  	3272	126026	126080	55
  	3273	126097	126115	19
  	3274	126130	126149	20
  	3275	126151	126179	29
  	3276	126186	126238	53
  	3277	126241	126279	39
  	3278	126275	126295	21
  	3279	126297	126312	16
  	3280	126320	126363	44
  	3281	126376	126395	20
  	3282	126406	126419	14
  	3283	126420	126442	23
  	3284	126467	126501	35
  	3285	126503	126538	36
  	3286	126566	126580	15
  	3287	126584	126597	14
  	3288	126620	126653	34
  	3289	126654	126694	41
  	3290	126697	126715	19
  	3291	126764	126777	14
  	3292	126792	126828	37
  	3293	126842	126862	21
  	3294	126866	126879	14
  	3295	126881	126897	17
  	3296	126906	126925	20
  	3297	126956	126987	32
  	3298	126989	127023	35
  	3299	127026	127135	110
  	3300	127142	127174	33
  	3301	127176	127191	16
  	3302	127193	127217	25
  	3303	127229	127253	25
  	3304	127255	127280	26
  	3305	127294	127394	101
  	3306	127396	127415	20
  	3307	127417	127478	62
  	3308	127491	127504	14
  	3309	127506	127530	25
  	3310	127542	127566	25
  	3311	127582	127628	47
  	3312	127654	127675	22
  	3313	127681	127706	26
  	3314	127706	127739	34
  	3315	127769	127792	24
  	3316	127808	127829	22
  	3317	127839	127888	50
  	3318	127900	127932	33
  	3319	127943	127975	33
  	3320	127988	128046	59
  	3321	128048	128069	22
  	3322	128068	128106	39
  	3323	128105	128118	14
  	3324	128121	128157	37
  	3325	128159	128188	30
  	3326	128190	128268	79
  	3327	128279	128317	39
  	3328	128321	128335	15
  	3329	128342	128368	27
  	3330	128374	128446	73
  	3331	128444	128540	97
  	3332	128546	128586	41
  	3333	128588	128640	53
  	3334	128642	128674	33
  	3335	128675	128879	205
  	3336	128881	128936	56
  	3337	128934	129000	67
  	3338	129002	129060	59
  	3339	129074	129100	27
  	3340	129107	129123	17
  	3341	129125	129163	39
  	3342	129168	129230	63
  	3343	129264	129277	14
  	3344	129284	129318	35
  	3345	129320	129346	27
  	3346	129357	129391	35
  	3347	129393	129420	28
  	3348	129447	129485	39
  	3349	129489	129504	16
  	3350	129514	129540	27
  	3351	129550	129563	14
  	3352	129559	129595	37
  	3353	129606	129627	22
  	3354	129633	129681	49
  	3355	129683	129697	15
  	3356	129699	129716	18
  	3357	129706	129738	33
  	3358	129757	129790	34
  	3359	129792	129820	29
  	3360	129812	129846	35
  	3361	129851	129867	17
  	3362	129869	129883	15
  	3363	129885	129915	31
  	3364	129917	129955	39
  	3365	129957	130046	90
  	3366	130042	130070	29
  	3367	130110	130156	47
  	3368	130158	130309	152
  	3369	130311	130373	63
  	3370	130375	130391	17
  	3371	130407	130429	23
  	3372	130439	130461	23
  	3373	130475	130507	33
  	3374	130512	130550	39
  	3375	130552	130582	31
  	3376	130584	130614	31
  	3377	130616	130764	149
  	3378	130766	130869	104
  	3379	130871	131021	151
  	3380	131033	131051	19
  	3381	131092	131105	14
  	3382	131112	131188	77
  	3383	131194	131237	44
  	3384	131233	131247	15
  	3385	131236	131287	52
  	3386	131292	131307	16
  	3387	131314	131333	20
  	3388	131373	131386	14
  	3389	131396	131417	22
  	3390	131419	131439	21
  	3391	131429	131458	30
  	3392	131481	131499	19
  	3393	131676	131689	14
  	3394	131729	131743	15
  	3395	131745	131764	20
  	3396	131785	131807	23
  	3397	131809	131875	67
  	3398	131877	131953	77
  	3399	131955	131980	26
  	3400	132020	132068	49
  	3401	132086	132108	23
  	3402	132118	132138	21
  	3403	132152	132183	32
  	3404	132185	132205	21
  	3405	132219	132232	14
  	3406	132234	132252	19
  	3407	132261	132291	31
  	3408	132319	132337	19
  	3409	132345	132363	19
  	3410	132365	132378	14
  	3411	132414	132483	70
  	3412	132504	132547	44
  	3413	132549	132582	34
  	3414	132584	132602	19
  	3415	132616	132642	27
  	3416	132643	132681	39
  	3417	132685	132714	30
  	3418	132736	132769	34
  	3419	132771	132793	23
  	3420	132809	132825	17
  	3421	132827	132841	15
  	3422	132861	132884	24
  	3423	132882	132900	19
  	3424	132899	132915	17
  	3425	132917	132951	35
  	3426	132940	132954	15
  	3427	132958	132983	26
  	3428	132985	133031	47
  	3429	133032	133051	20
  	3430	133042	133060	19
  	3431	133051	133071	21
  	3432	133073	133087	15
  	3433	133083	133104	22
  	3434	133097	133110	14
  	3435	133131	133199	69
  	3436	133198	133222	25
  	3437	133233	133249	17
  	3438	133251	133284	34
  	3439	133327	133429	103
  	3440	133431	133596	166
  	3441	133588	133602	15
  	3442	133598	133611	14
  	3443	133613	133628	16
  	3444	133628	133646	19
  	3445	133651	133670	20
  	3446	133666	133707	42
  	3447	133718	133742	25
  	3448	133743	133777	35
  	3449	133779	133794	16
  	3450	133821	133851	31
  	3451	133859	133880	22
  	3452	133890	133921	32
  	3453	133923	133974	52
  	3454	133982	133998	17
  	3455	134000	134036	37
  	3456	134065	134107	43
  	3457	134120	134173	54
  	3458	134165	134179	15
  	3459	134187	134200	14
  	3460	134207	134242	36
  	3461	134244	134258	15
  	3462	134260	134273	14
  	3463	134275	134299	25
  	3464	134314	134346	33
  	3465	134356	134371	16
  	3466	134365	134380	16
  	3467	134374	134420	47
  	3468	134445	134477	33
  	3469	134508	134523	16
  	3470	134531	134548	18
  	3471	134542	134555	14
  	3472	134568	134621	54
  	3473	134647	134667	21
  	3474	134679	134719	41
  	3475	134721	134824	104
  	3476	134826	134849	24
  	3477	134856	134869	14
  	3478	134877	134910	34
  	3479	134912	134966	55
  	3480	134960	134980	21
  	3481	134989	135012	24
  	3482	135014	135066	53
  	3483	135074	135093	20
  	3484	135108	135125	18
  	3485	135151	135260	110
  	3486	135264	135277	14
  	3487	135273	135310	38
  	3488	135321	135337	17
  	3489	135340	135365	26
  	3490	135360	135374	15
  	3491	135364	135386	23
  	3492	135388	135430	43
  	3493	135432	135447	16
  	3494	135498	135521	24
  	3495	135519	135545	27
  	3496	135559	135622	64
  	3497	135624	135647	24
  	3498	135656	135673	18
  	3499	135675	135704	30
  	3500	135721	135742	22
  	3501	135753	135796	44
  	3502	135815	135858	44
  	3503	135860	135880	21
  	3504	135883	135915	33
  	3505	135922	135965	44
  	3506	135979	135993	15
  	3507	135995	136036	42
  	3508	136051	136065	15
  	3509	136108	136165	58
  	3510	136173	136190	18
  	3511	136192	136287	96
  	3512	136289	136303	15
  	3513	136317	136346	30
  	3514	136375	136415	41
  	3515	136429	136470	42
  	3516	136472	136496	25
  	3517	136498	136532	35
  	3518	136542	136565	24
  	3519	136643	136657	15
  	3520	136674	136701	28
  	3521	136704	136719	16
  	3522	136715	136728	14
  	3523	136721	136737	17
  	3524	136737	136750	14
  	3525	136783	136810	28
  	3526	136824	136849	26
  	3527	136859	136896	38
  	3528	136898	136927	30
  	3529	136949	136983	35
  	3530	136985	137000	16
  	3531	137053	137071	19
  	3532	137077	137097	21
  	3533	137108	137164	57
  	3534	137166	137196	31
  	3535	137198	137221	24
  	3536	137223	137267	45
  	3537	137276	137359	84
  	3538	137360	137385	26
  	3539	137393	137440	48
  	3540	137438	137496	59
  	3541	137498	137518	21
  	3542	137523	137536	14
  	3543	137539	137572	34
  	3544	137584	137612	29
  	3545	137614	137628	15
  	3546	137630	137644	15
  	3547	137646	137669	24
  	3548	137702	137727	26
  	3549	137731	137745	15
  	3550	137759	137772	14
  	3551	137784	137819	36
  	3552	137832	137858	27
  	3553	137861	137876	16
  	3554	137878	137900	23
  	3555	137909	137925	17
  	3556	137924	137961	38
  	3557	137968	137981	14
  	3558	138011	138033	23
  	3559	138035	138077	43
  	3560	138079	138097	19
  	3561	138224	138238	15
  	3562	138232	138252	21
  	3563	138242	138256	15
  	3564	138255	138284	30
  	3565	138295	138326	32
  	3566	138328	138357	30
  	3567	138359	138389	31
  	3568	138403	138449	47
  	3569	138451	138492	42
  	3570	138500	138515	16
  	3571	138524	138548	25
  	3572	138555	138568	14
  	3573	138571	138589	19
  	3574	138589	138629	41
  	3575	138644	138680	37
  	3576	138697	138710	14
  	3577	138712	138729	18
  	3578	138744	138761	18
  	3579	138776	138801	26
  	3580	138860	138896	37
  	3581	138898	138923	26
  	3582	138925	138965	41
  	3583	138967	139008	42
  	3584	139010	139031	22
  	3585	139029	139043	15
  	3586	139034	139048	15
  	3587	139041	139056	16
  	3588	139055	139074	20
  	3589	139078	139094	17
  	3590	139084	139098	15
  	3591	139092	139116	25
  	3592	139133	139147	15
  	3593	139154	139173	20
  	3594	139175	139192	18
  	3595	139204	139229	26
  	3596	139231	139255	25
  	3597	139257	139270	14
  	3598	139272	139303	32
  	3599	139315	139335	21
  	3600	139337	139372	36
  	3601	139383	139397	15
  	3602	139399	139419	21
  	3603	139423	139437	15
  	3604	139435	139492	58
  	3605	139501	139518	18
  	3606	139508	139521	14
  	3607	139571	139586	16
  	3608	139588	139622	35
  	3609	139636	139655	20
  	3610	139657	139673	17
  	3611	139685	139699	15
  	3612	139724	139795	72
  	3613	139796	139811	16
  	3614	139818	139834	17
  	3615	139836	139857	22
  	3616	139856	139869	14
  	3617	139859	139882	24
  	3618	139891	139920	30
  	3619	139930	139952	23
  	3620	139965	139980	16
  	3621	139982	140011	30
  	3622	140013	140031	19
  	3623	140047	140072	26
  	3624	140074	140099	26
  	3625	140101	140119	19
  	3626	140121	140135	15
  	3627	140144	140158	15
  	3628	140157	140183	27
  	3629	140185	140210	26
  	3630	140231	140262	32
  	3631	140258	140272	15
  	3632	140264	140288	25
  	3633	140290	140325	36
  	3634	140339	140364	26
  	3635	140369	140402	34
  	3636	140428	140451	24
  	3637	140453	140510	58
  	3638	140512	140541	30
  	3639	140556	140621	66
  	3640	140626	140651	26
  	3641	140653	140724	72
  	3642	140726	140789	64
  	3643	140802	140825	24
  	3644	140837	140861	25
  	3645	140863	140896	34
  	3646	140903	140927	25
  	3647	140958	140993	36
  	3648	141001	141014	14
  	3649	141022	141053	32

• In some embodiments, the oligonucleotide comprises a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary, such as 100% complementarity, to a corresponding target nucleic acid region present in SEQ ID NO: 1, wherein the target nucleic acid region is selected from the group consisting of region B1 to B400 in table 2

• TABLE 2
  Regions of SEQ ID NO 1 which may be targeted
  using oligonucleotide of the invention

  	Position in
  	SEQ ID NO 1

  	Reg.	To	From	Length

  	B1	225	238	14
  	B2	1163	1178	16
  	B3	2526	2539	14
  	B4	2805	2820	16
  	B5	3027	3040	14
  	B6	3208	3222	15
  	B7	3212	3225	14
  	B8	3228	3241	14
  	B9	3243	3256	14
  	B10	3810	3854	45
  	B11	4664	4680	17
  	B12	5516	5529	14
  	B13	5657	5671	15
  	B14	5661	5676	16
  	B15	5964	5977	14
  	B16	6217	6234	18
  	B17	6224	6237	14
  	B18	6408	6422	15
  	B19	7300	7313	14
  	B20	7399	7412	14
  	B21	7541	7564	24
  	B22	7626	7640	15
  	B23	7662	7694	33
  	B24	7791	7806	16
  	B25	7853	7868	16
  	B26	8206	8219	14
  	B27	8443	8456	14
  	B28	8739	8752	14
  	B29	9197	9212	16
  	B30	10189	10203	15
  	B31	10754	10768	15
  	B32	10758	10771	14
  	B33	11790	11803	14
  	B34	11870	11883	14
  	B35	11993	12007	15
  	B36	B11996	12011	16
  	B37	12017	12040	24
  	B38	12095	12108	14
  	B39	12345	12358	14
  	B40	12721	12734	14
  	B41	13372	13386	15
  	B42	13489	13505	17
  	B43	15576	15590	15
  	B44	15617	15632	16
  	B45	15840	15853	14
  	B46	16041	16054	14
  	B47	16207	16222	16
  	B48	16308	16321	14
  	B49	16349	16362	14
  	B50	16463	16479	17
  	B51	16528	16542	15
  	B52	16543	16556	14
  	B53	20495	20508	14
  	B54	20617	20630	14
  	B55	20960	20977	18
  	B56	21465	21479	15
  	B57	21491	21508	18
  	B58	23479	23496	18
  	B59	23741	23755	15
  	B60	25236	25249	14
  	B61	25323	25336	14
  	B62	25447	25462	16
  	B63	25588	25601	14
  	B64	25853	25867	15
  	B65	25885	25898	14
  	B66	26280	26293	14
  	B67	26388	26404	17
  	B68	26416	26450	35
  	B69	26687	26702	16
  	B70	26706	26719	14
  	B71	26783	26796	14
  	B72	27039	27052	14
  	B73	27251	27265	15
  	B74	28683	28698	16
  	B75	29302	29315	14
  	B76	29304	29317	14
  	B77	29308	29321	14
  	B78	29532	29545	14
  	B79	29974	29987	14
  	B80	30054	30068	15
  	B81	30267	30281	15
  	B82	30623	30638	16
  	B83	30628	30641	14
  	B84	30814	30827	14
  	B85	30881	30894	14
  	B86	32459	32478	20
  	B87	37299	37315	17
  	B88	39083	39096	14
  	B89	39370	39383	14
  	B90	39659	39672	14
  	B91	40814	40831	18
  	B92	40851	40864	14
  	B93	41782	41795	14
  	B94	41873	41886	14
  	B95	42037	42050	14
  	B96	42048	42063	16
  	B97	42096	42116	21
  	B98	42959	42973	15
  	B99	43165	43178	14
  	B100	45926	45939	14
  	B101	48163	48176	14
  	B102	52732	52745	14
  	B103	52984	53015	32
  	B104	54404	54420	17
  	B105	55294	55320	27
  	B106	55337	55350	14
  	B107	55420	55434	15
  	B108	55487	55501	15
  	B109	55623	55638	16
  	B110	56195	56214	20
  	B111	56584	56597	14
  	B112	57267	57282	16
  	B113	58126	58139	14
  	B114	58170	58183	14
  	B115	58295	58309	15
  	B116	58658	58671	14
  	B117	58906	58921	16
  	B118	58988	59005	18
  	B119	59024	59045	22
  	B120	59191	59207	17
  	B121	59236	59251	16
  	B122	59298	59312	15
  	B123	59358	59378	21
  	B124	59400	59413	14
  	B125	59434	59447	14
  	B126	59589	59602	14
  	B127	59620	59642	23
  	B128	59718	59743	26
  	B129	59826	59841	16
  	B130	59843	59864	22
  	B131	59882	59906	25
  	B132	59930	59958	29
  	B133	59959	60004	46
  	B134	60006	60029	24
  	B135	60033	60071	39
  	B136	60139	60171	33
  	B137	60193	60215	23
  	B138	60212	60225	14
  	B139	60231	60244	14
  	B140	60246	60265	20
  	B141	60267	60282	16
  	B142	60292	60309	18
  	B143	60348	60361	14
  	B144	60358	60429	72
  	B145	60427	60517	91
  	B146	60519	60545	27
  	B147	60557	60575	19
  	B148	60580	60593	14
  	B149	60595	60622	28
  	B150	60675	60690	16
  	B151	60697	60713	17
  	B152	60727	60754	28
  	B153	60756	60799	44
  	B154	60801	60817	17
  	B155	60819	60855	37
  	B156	61423	61436	14
  	B157	61592	61605	14
  	B158	61624	61637	14
  	B159	61673	61713	41
  	B160	61715	61731	17
  	B161	61733	61752	20
  	B162	61769	61794	26
  	B163	61805	61825	21
  	B164	62101	62114	14
  	B165	62302	62315	14
  	B166	62436	62449	14
  	B167	62664	62679	16
  	B168	62993	63006	14
  	B169	63098	63111	14
  	B170	63347	63367	21
  	B171	63371	63396	26
  	B172	63385	63398	14
  	B173	63526	63539	14
  	B174	65032	65045	14
  	B175	66556	66569	14
  	B176	67158	67183	26
  	B177	67181	67194	14
  	B178	68007	68021	15
  	B179	68644	68657	14
  	B180	69294	69317	24
  	B181	69306	69323	18
  	B182	69353	69366	14
  	B183	70497	70511	15
  	B184	71600	71613	14
  	B185	71887	71905	19
  	B186	72259	72272	14
  	B187	72589	72602	14
  	B188	72783	72796	14
  	B189	73528	73541	14
  	B190	73783	73800	18
  	B191	74907	74920	14
  	B192	75965	75981	17
  	B193	75983	75998	16
  	B194	76004	76020	17
  	B195	76110	76166	57
  	B196	76186	76205	20
  	B197	76234	76253	20
  	B198	76261	76280	20
  	B199	76369	76382	14
  	B200	77139	77152	14
  	B201	77409	77422	14
  	B202	77478	77524	47
  	B203	77526	77590	65
  	B204	77628	77641	14
  	B205	77688	77701	14
  	B206	78275	78308	34
  	B207	78310	78332	23
  	B208	78340	78356	17
  	B209	78358	78371	14
  	B210	78373	78395	23
  	B211	78397	78440	44
  	B212	78442	78455	14
  	B213	78475	78489	15
  	B214	78696	78709	14
  	B215	78847	78860	14
  	B216	79493	79516	24
  	B217	79705	79718	14
  	B218	81009	81054	46
  	B219	81353	81367	15
  	B220	81970	81986	17
  	B221	81991	82006	16
  	B222	82042	82106	65
  	B223	82278	82291	14
  	B224	82716	82735	20
  	B225	84314	84328	15
  	B226	85628	85665	38
  	B227	86226	86239	14
  	B228	86237	86253	17
  	B229	86566	86579	14
  	B230	86945	86959	15
  	B231	87337	87358	22
  	B232	87662	87675	14
  	B233	89424	89439	16
  	B234	89972	89985	14
  	B235	90782	90795	14
  	B236	90939	90953	15
  	B237	90942	90955	14
  	B238	90965	90981	17
  	B239	91101	91115	15
  	B240	92083	92096	14
  	B241	92164	92177	14
  	B242	92179	92192	14
  	B243	92194	92210	17
  	B244	92212	92236	25
  	B245	92245	92260	16
  	B246	92262	92302	41
  	B247	92304	92321	18
  	B248	92323	92366	44
  	B249	92375	92389	15
  	B250	92392	92405	14
  	B251	92407	92426	20
  	B252	92442	92459	18
  	B253	92497	92516	20
  	B254	92578	92591	14
  	B255	92599	92612	14
  	B256	92614	92651	38
  	B257	92659	92684	26
  	B258	92686	92699	14
  	B259	92704	92726	23
  	B260	92731	92750	20
  	B261	92752	92774	23
  	B262	92780	92795	16
  	B263	92800	92813	14
  	B264	92839	92858	20
  	B265	92860	92891	32
  	B266	92893	92906	14
  	B267	92908	92921	14
  	B268	92923	92941	19
  	B269	92965	92986	22
  	B270	92988	93002	15
  	B271	93044	93059	16
  	B272	93061	93076	16
  	B273	93105	93122	18
  	B274	93142	93209	68
  	B275	93227	93241	15
  	B276	93288	93305	18
  	B277	93325	93344	20
  	B278	93398	93412	15
  	B279	93572	93586	15
  	B280	94509	94522	14
  	B281	95720	95738	19
  	B282	97050	97065	16
  	B283	97079	97098	20
  	B284	97127	97194	68
  	B285	97208	97230	23
  	B286	97232	97284	53
  	B287	97286	97311	26
  	B288	97313	97362	50
  	B289	97368	97383	16
  	B290	97426	97439	14
  	B291	98077	98090	14
  	B292	98227	98240	14
  	B293	98232	98255	24
  	B294	99151	99164	14
  	B295	99405	99418	14
  	B296	99570	99583	14
  	B297	99733	99748	16
  	B298	101829	101842	14
  	B299	101882	101895	14
  	B300	101955	101968	14
  	B301	102202	102215	14
  	B302	103310	103325	16
  	B303	103653	103666	14
  	B304	103908	103923	16
  	B305	103912	103928	17
  	B306	103917	103933	17
  	B307	104971	104984	14
  	B308	105217	105230	14
  	B309	105233	105250	18
  	B310	105443	105457	15
  	B311	105544	105559	16
  	B312	106047	106071	25
  	B313	106061	106074	14
  	B314	106093	106107	15
  	B315	106114	106130	17
  	B316	106243	106256	14
  	B317	106251	106264	14
  	B318	106840	106855	16
  	B319	108113	108130	18
  	B320	108325	108338	14
  	B321	108856	108869	14
  	B322	109109	109122	14
  	B323	109113	109127	15
  	B324	109116	109132	17
  	B325	110301	110314	14
  	B326	110315	110328	14
  	B327	110317	110330	14
  	B328	112528	112546	19
  	B329	112607	112620	14
  	B330	114775	114788	14
  	B331	116322	116335	14
  	B332	116968	116981	14
  	B333	117788	117801	14
  	B334	118034	118057	24
  	B335	118230	118246	17
  	B336	118235	118248	14
  	B337	118870	118883	14
  	B338	119755	119784	30
  	B339	119786	119800	15
  	B340	120363	120406	44
  	B341	120504	120517	14
  	B342	121161	121174	14
  	B343	121330	121347	18
  	B344	121338	121351	14
  	B345	123417	123430	14
  	B346	123464	123481	18
  	B347	125026	125042	17
  	B348	127046	127071	26
  	B349	127090	127103	14
  	B350	127311	127324	14
  	B351	127354	127367	14
  	B352	127363	127379	17
  	B353	127399	127412	14
  	B354	127863	127876	14
  	B355	128134	128148	15
  	B356	128280	128310	31
  	B357	128343	128368	26
  	B358	128444	128457	14
  	B359	128446	128469	24
  	B360	128498	128511	14
  	B361	128511	128524	14
  	B362	129892	129905	14
  	B363	130261	130283	23
  	B364	130375	130388	14
  	B365	130415	130428	14
  	B366	130634	130650	17
  	B367	130667	130717	51
  	B368	130719	130764	46
  	B369	130783	130796	14
  	B370	130798	130820	23
  	B371	130840	130861	22
  	B372	130975	130994	20
  	B373	131112	131132	21
  	B374	131142	131161	20
  	B375	131233	131246	14
  	B376	131729	131743	15
  	B377	132754	132767	14
  	B378	132924	132937	14
  	B379	133174	133190	17
  	B380	133198	133212	15
  	B381	133207	133222	16
  	B382	133476	133489	14
  	B383	133479	133492	14
  	B384	133491	133531	41
  	B385	133533	133550	18
  	B386	133555	133594	40
  	B387	134160	134173	14
  	B388	134165	134178	14
  	B389	134533	134546	14
  	B390	136724	136737	14
  	B391	137438	137463	26
  	B392	137878	137891	14
  	B393	138082	138097	16
  	B394	138233	138252	20
  	B395	138930	138943	14
  	B396	138947	138960	14
  	B397	138950	138963	14
  	B398	139502	139518	17
  	B399	139508	139521	14
  	B400	140978	140991	14

• In certain embodiments the oligonucleotide or contiguous nucleotide sequence is complementary to a region (or sub-sequence)(or sub-sequence) of the target nucleic acid, wherein the target nucleic acid region is selected from the group consisting of position 1589-10889, 46089-53989 and 60789-62489 of SEQ ID NO: 1.
• In one embodiment the oligonucleotide comprises a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90%, such as 100% complementary to a target nucleic acid sequence of position 55319 to 141053 of SEQ ID NO: 1.
• In one embodiment the oligonucleotide comprises a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90%, such as 100% complementary to a target nucleic acid sequence of position 1 to 55318 of SEQ ID NO: 1.
• In some embodiments, the oligonucleotide comprises a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid selected from the group corresponding to positions: 55319-76274, 77483-77573, 92157-93403 and 97056-97354 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid selected from the group corresponding to positions: 60821-60849, 77567-77583, 92323-92339 and 97156-97172 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions: 5218-5240 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions: 5782-5803 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions: 8113-8139 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions: 9200-9250 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions: 11505-11555 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions: 13223-13242 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions 15100-15150 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions 15113-15180 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions 29635-29705 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions 30590-30740 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid corresponding to positions 39800-39855 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid to positions 44435-44460 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid to positions 45245-45270 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid to positions 46380-46430 of SEQ ID NO: 1.
• In some embodiments the oligonucleotide a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 90% complementary to a sub-sequence of the target nucleic acid to positions 68915-68940 of SEQ ID NO: 1.
• In some embodiments, the oligonucleotide comprises or consists of 8 to 35 nucleotides in length, such as from 10 to 30, such as 11 to 22, such as from 12 to 18, such as from 13 to 17 or 14 to 16 contiguous nucleotides in length. In a preferred embodiment, the oligonucleotide comprises or consists of 15 to 20 nucleotides in length.
• In some embodiments, the oligonucleotide or contiguous nucleotide sequence thereof comprises or consists of 22 or less nucleotides, such as 20 or less nucleotides, such as 18 or less nucleotides, such as 14, 15, 16 or 17 nucleotides. It is to be understood that any range given herein includes the range endpoints. Accordingly, if an oligonucleotide is said to include from 10 to 30 nucleotides, both 10 and 30 nucleotides are included.
• In some embodiments, the contiguous nucleotide sequence comprises or consists of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 contiguous nucleotides in length. In a preferred embodiment, the oligonucleotide comprises or consists of 16, 17, 18 or 19 nucleotides in length.
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 4 to 150 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 4 to 818 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 4 to 678 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 166, 167, 167 or 169 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 570, 571, 572, 679, 680, 681, 682 and 683 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 34, 186, 187, 188, 573, 574, 575, 576, 572, 684, 685, 686, 687, 688, 689, 690, 691, 692, 963, 964, 965 and 696 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 35, 199, 200, 201, 202, 203, 204, 205, 206, 207, 209 and 210 or SEQ ID NO: 582, 583 and 584 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 221, 222, 223, 224, 225, 585, 586, 587, 588, 589, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717 and 718 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 236, 237, 238, 239, 240 and 590.
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 241, 591 and 719 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 46, 47, 48, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 800, 800, 800, 800, 801, 801, 802, 803, 804, 805, 806 and 807 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 331, 332, 638, 639, 640, 808, 809, 810, 811, 812, 813, 814 and 815 (see motif sequences listed in table 3 in the Examples section).
• In some embodiments, the antisense oligonucleotide or contiguous nucleotide sequence comprises or consists of 10 to 30 nucleotides in length with at least 90% identity, preferably 100% identity to a sequence selected from the group consisting of SEQ ID NO: 409, 410, 411, 642, 643, 644, 645, 646, 816, 818 and 818 (see motif sequences listed in table 3 in the Examples section).
• It is understood that the contiguous nucleobase sequences (motif sequence) can be modified to for example increase nuclease resistance and/or binding affinity to the target nucleic acid. Modifications are described in the definitions and in the “Oligonucleotide design” section. Table 3 lists preferred designs of each motif sequence.
Oligonucleotide Design
• Oligonucleotide design refers to the pattern of nucleoside sugar modifications in the oligonucleotide sequence. The oligonucleotides of the invention comprise sugar-modified nucleosides and may also comprise DNA or RNA nucleosides. In some embodiments, the oligonucleotide comprises sugar-modified nucleosides and DNA nucleosides. Incorporation of modified nucleosides into the oligonucleotide of the invention may enhance the affinity of the oligonucleotide for the target nucleic acid. In that case, the modified nucleosides can be referred to as affinity enhancing modified nucleotides.
• In an embodiment, the oligonucleotide comprises at least 1 modified nucleoside, such as at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 16 modified nucleosides. In an embodiment the oligonucleotide comprises from 1 to 10 modified nucleosides, such as from 2 to 9 modified nucleosides, such as from 3 to 8 modified nucleosides, such as from 4 to 7 modified nucleosides, such as 6 or 7 modified nucleosides. In some embodiments, at least 1 of the modified nucleosides is a locked nucleic acid (LNA), such as at least 2, such as at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 of the modified nucleosides are LNA. In a still further embodiment all the modified nucleosides are LNA.
• In an embodiment, the oligonucleotide of the invention may comprise modifications, which are independently selected from these three types of modifications (modified sugar, modified nucleobase and modified internucleoside linkage) or a combination thereof. Preferably the oligonucleotide comprises one or more sugar modified nucleosides, such as 2′ sugar modified nucleosides. Preferably the oligonucleotide of the invention comprise the one or more 2′ sugar modified nucleoside independently selected from the group consisting of 2′-O-alkyl-RNA, 2′-O-methyl-RNA, 2′-alkoxy-RNA, 2′-O-methoxyethyl-RNA, 2′-amino-DNA, 2′-fluoro-DNA, arabino nucleic acid (ANA), 2′-fluoro-ANA and LNA nucleosides. Even more preferably the one or more modified nucleoside is LNA.
• In a further embodiment the oligonucleotide comprises at least one modified internucleoside linkage. In a preferred embodiment the internucleoside linkages within the contiguous nucleotide sequence are phosphorothioate or boranophosphate internucleoside linkages.
• In some embodiments, the oligonucleotide of the invention comprise at least one modified nucleoside which is a 2′-MOE-RNA, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 2′-MOE-RNA nucleoside units. In some embodiments, at least one of said modified nucleoside is 2′-fluoro DNA, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 2′-fluoro-DNA nucleoside units.
• In some embodiments, the oligonucleotide of the invention comprises at least one LNA unit, such as 1, 2, 3, 4, 5, 6, 7, or 8 LNA units, such as from 2 to 6 LNA units, such as from 3 to 7 LNA units, 4 to 8 LNA units or 3, 4, 5, 6 or 7 LNA units. In some embodiments, all the modified nucleosides are LNA nucleosides. In a further embodiment, the oligonucleotide may comprise both beta-D-oxy-LNA, and one or more of the following LNA units: thio-LNA, amino-LNA, oxy-LNA, and/or ENA in either the beta-D or alpha-L configurations or combinations thereof. In a further embodiment, all LNA cytosine units are 5-methyl-cytosine. In a preferred embodiment the oligonucleotide or contiguous nucleotide sequence has at least 1 LNA unit at the 5′ end and at least 2 LNA units at the 3′ end of the nucleotide sequence.
• In some embodiments, the oligonucleotide of the invention comprises at least one LNA unit and at least one 2′ substituted modified nucleoside.
• In some embodiments of the invention, the oligonucleotide comprise both 2′ sugar modified nucleosides and DNA units. Preferably the oligonucleotide comprise both LNA and DNA units. Preferably, the combined total of LNA and DNA units is 8-30, such as 10-25, preferably 12-22, such as 12-18, even more preferably 11-16. In some embodiments of the invention, the nucleotide sequence of the oligonucleotide, such as the contiguous nucleotide sequence consists of at least one or two LNA units and the remaining nucleotide units are DNA units. In some embodiments the oligonucleotide comprises only LNA nucleosides and naturally occurring nucleosides (such as RNA or DNA, most preferably DNA nucleosides), optionally with modified internucleoside linkages such as phosphorothioate.
• In an embodiment of the invention the oligonucleotide of the invention is capable of recruiting RNase H.
Gapmer Design
• In a preferred embodiment the oligonucleotide of the invention has a gapmer design or structure also referred herein merely as “Gapmer”. In a gapmer structure the oligonucleotide comprises at least three distinct structural regions a 5′-flank, a gap and a 3′-flank, F-G-F′ in ′5->3′ orientation. In this design, flanking regions F and F′ (also termed wing regions) comprise a contiguous stretch of modified nucleosides, which are complementary to the UBE3A target nucleic acid, while the gap region, G, comprises a contiguous stretch of nucleotides which are capable of recruiting a nuclease, preferably an endonuclease such as RNase, for example RNase H, when the oligonucleotide is in duplex with the target nucleic acid. Nucleosides which are capable of recruiting a nuclease, in particular RNase H, can be selected from the group consisting of DNA, alpha-L-oxy-LNA, 2′-Flouro-ANA and UNA. Regions F and F′, flanking the 5′ and 3′ ends of region G, preferably comprise non-nuclease recruiting nucleosides (nucleosides with a 3′ endo structure), more preferably one or more affinity enhancing modified nucleosides. In some embodiments, the 3′ flank comprises at least one LNA nucleoside, preferably at least 2 LNA nucleosides. In some embodiments, the 5′ flank comprises at least one LNA nucleoside. In some embodiments both the 5′ and 3′ flanking regions comprise a LNA nucleoside. In some embodiments all the nucleosides in the flanking regions are LNA nucleosides. In other embodiments, the flanking regions may comprise both LNA nucleosides and other nucleosides (mixed flanks), such as DNA nucleosides and/or non-LNA modified nucleosides, such as 2′ substituted nucleosides. In this case the gap is defined as a contiguous sequence of at least 5 RNase H recruiting nucleosides (nucleosides with a 2′ endo structure, preferably DNA) flanked at the 5′ and 3′ end by an affinity enhancing modified nucleoside, preferably LNA, such as beta-D-oxy-LNA. Consequently, the nucleosides of the 5′ flanking region and the 3′ flanking region which are adjacent to the gap region are modified nucleosides, preferably non-nuclease recruiting nucleosides. In oligonucleotides with mixed flanks where the flanks comprise DNA the 5′ and 3′ nucleosides are modified nucleosides.
Region F
• Region F (5′ flank or 5′ wing) attached to the ′5 end of region G comprises, contains or consists of at least one modified nucleoside such as at least 2, at least 3, at least 4, at least 5, at least 6, at least 7 modified nucleosides. In an embodiment region F comprises or consists of from 1 to 7 modified nucleosides, such as from 2 to 6 modified nucleosides, such as from 2 to 5 modified nucleosides, such as from 2 to 4 modified nucleosides, such as from 1 to 3 modified nucleosides, such as 1, 2, 3 or 4 modified nucleosides. In a further embodiment further additional nucleosides may be attached to the ′5 end of region F, representing a region D preferably comprising 1, 2 or 3 nucleoside units, such as DNA nucleosides. Region D can take the function of a biocleavable (B) linker described in the definition of “Linkers”.
• In some embodiments, the modified nucleosides in region F have a 3′ endo structure.
• In an embodiment, one or more of the modified nucleosides in region F are 2′ modified nucleosides.
• In a further embodiment one or more of the 2′ modified nucleosides in region F are selected from 2′-O-alkyl-RNA units, 2′-O-methyl-RNA, 2′-amino-DNA units, 2′-fluoro-DNA units, 2′-alkoxy-RNA, MOE units, LNA units, arabino nucleic acid (ANA) units and 2′-fluoro-ANA units.
• In one embodiment of the invention all the modified nucleosides in region F are LNA nucleosides. In a further embodiment the LNA nucleosides in region F are independently selected from the group consisting of oxy-LNA, thio-LNA, amino-LNA, cET, and/or ENA, in either the beta-D or alpha-L configurations or combinations thereof. In a preferred embodiment region F has at least 1 beta-D-oxy LNA unit, at the 5′ end of the contiguous sequence.
Region G
• Region G (gap region) preferably comprise, contain or consist of at least 4, such as at least 5, such as at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 16 consecutive nucleosides capable of recruiting the aforementioned nuclease, in particular RNaseH. In a further embodiment region G comprise, contain or consist of from 5 to 12, or from 6 to 10 or from 7 to 9, such as 8 consecutive nucleotide units capable of recruiting aforementioned nuclease.
• The nucleoside units in region G, which are capable of recruiting nuclease are in an embodiment selected from the group consisting of DNA, alpha-L-LNA, C4′ alkylated DNA (as described in PCT/EP2009/050349 and Vester et al., Bioorg. Med. Chem. Lett. 18 (2008) 2296-2300, both incorporated herein by reference), arabinose derived nucleosides like ANA and 2′F-ANA (Mangos et al. 2003 J. AM. CHEM. SOC. 125, 654-661), UNA (unlocked nucleic acid) (as described in Fluiter et al., Mol. Biosyst., 2009, 10, 1039 incorporated herein by reference). UNA is unlocked nucleic acid, typically where the bond between C2 and C3 of the ribose has been removed, forming an unlocked “sugar” residue.
• In a still further embodiment at least one nucleoside unit in region G is a DNA nucleoside unit, such as from 1 to 16 DNA units, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 DNA units, preferably from 2 to 13 DNA units, such as from 4 to 12 DNA units, more preferably from 5 to 11, or from 10 to 16, 11 to 15 or 12 to 14 DNA units. In some embodiments, region G consists of 100% DNA units. In a preferred embodiment G consists of, most preferably 10, 11, 12, 13, 14 or 15 DNA units.
• In further embodiments the region G may consist of a mixture of DNA and other nucleosides capable of mediating RNase H cleavage. Region G may consist of at least 50% DNA, more preferably 60%, 70% or 80% DNA, and even more preferred 90% or 95% DNA.
• In a still further embodiment at least one nucleoside unit in region G is an alpha-L-LNA nucleoside unit, such as at least one alpha-L-LNA unit, such as 2, 3, 4, 5, 6, 7, 8 or 9 alpha-L-LNA units. In a further embodiment, region G comprises the least one alpha-L-LNA is alpha-L-oxy-LNA unit. In a further embodiment region G comprises a combination of DNA and alpha-L-LNA nucleoside units.
• In some embodiments the size of the contiguous sequence in region G may be longer, such as 15, 16, 17, 18, 19 or 20 nucleoside units.
• In some embodiments, nucleosides in region G have a 2′ endo structure.
Region F′
• Region F′ (3′ flank or 3′ wing) attached to the ′3 end of region G comprises, contains or consists of at least one modified nucleoside such as at least 2, at least 3, at least 4, at least 5, at least 6, at least 7 modified nucleosides. In an embodiment region F′ comprise or consist of from 1 to 7 modified nucleosides, such as from 2 to 6 modified nucleoside, such as from 2 to 4 modified nucleosides, such as from 1 to 3 modified nucleosides, such as 1, 2, 3 or 4 modified nucleosides. In a further embodiment further additional nucleosides attached to the ′3 end of region F′, representing a region D′, preferably comprising 1, 2 or 3 nucleoside units, such as DNA nucleosides. Region D′ can take the function of a biocleavable (B) linker described, in the section “Linkers”.
• In some embodiments, the modified nucleosides in region F′ have a 3′ endo structure.
• In a preferred embodiment, modified nucleosides in region F′ is LNA.
• In a further embodiment modified nucleosides in region F′ are selected from 2′-O-alkyl-RNA units, 2′-O-methyl-RNA, 2′-amino-DNA units, 2′-fluoro-DNA units, 2′-alkoxy-RNA, MOE units, LNA units, arabino nucleic acid (ANA) units and 2′-fluoro-ANA units.
• In one embodiment of the invention all the modified nucleosides in region F′ are LNA nucleosides. In a further embodiment the LNA nucleosides in region F′ are independently selected from the group consisting of oxy-LNA, thio-LNA, amino-LNA, cET and/or ENA, in either the beta-D or alpha-L configurations or combinations thereof. In a preferred embodiment region F′ has at least 2 beta-D-oxy LNA unit, at the 3′ end of the contiguous sequence.
Region D and D′
• Region D and D′ can be attached to the 5′ end of region F or the 3′ end of region F′, respectively.
• Region D or D′ may independently comprise 1, 2, 3, 4 or 5 additional nucleotides, which may be complementary or non-complementary to the target nucleic acid. In this respect the oligonucleotide of the invention, may in some embodiments comprise a contiguous nucleotide sequence capable of modulating the target which is flanked at the 5′ and/or 3′ end by additional nucleotides. Such additional nucleotides may serve as a nuclease susceptible biocleavable linker (see definition of linkers). In some embodiments the additional 5′ and/or 3′ end nucleotides are linked with phosphodiester linkages, and may be DNA or RNA. In another embodiment, the additional 5′ and/or 3′ end nucleotides are modified nucleotides which may for example be included to enhance nuclease stability or for ease of synthesis. In an embodiment of the oligonucleotide of the invention, comprises a region D and/or D′ in addition to the contiguous nucleotide sequence.
• The gapmer oligonucleotide of the present invention can be represented by the following formulae:
• 
  F-G-F′; in particular F_1-7-G_4-12-F′_1-7
• 
  D-F-G-F′, in particular D_1-3-F_1-7-G_4-12-F′_1-7
• 
  F-G-F′-D′, in particular F_1-7-G_4-12-F′_1-7-D′_1-3
• 
  D-F-G-F′-D′, in particular D_1-3-F_1-7-G_4-12-F′_1-7-D′_1-3
• The preferred number and types of nucleosides in regions F, G and F′, D and D′ have been described above. The design of the individual oligonucleotide may also have profound impact on the properties of the oligonucleotide in its use for modulating expression of UBE3A.
• In some embodiments the oligonucleotide is a gapmer consisting of 14, 15, 16, 17, 18, 19 or 20 nucleotides in length, wherein each of regions F and F′ independently consists of 2, 3 or 4 modified nucleoside units complementary to a part of the human SNHG14 long non-coding RNA which is antisense to the UBE3A pre-mRNA (the target nucleic acid) and region G consists of 10, 11, 12, 13, 14 or 15 nucleoside units, capable of recruiting nuclease when in duplex with the target nucleic acid.
• In a further embodiments, the oligonucleotide is a gapmer wherein each of regions F and F′ independently consists of 2, 3, 4 or 5 modified nucleoside units, such as nucleoside units containing a 2′-O-methoxyethyl-ribose sugar (2′-MOE) or nucleoside units containing a 2′-fluoro-deoxyribose sugar and/or LNA units, and region G consists of 9, 10, 11, 12, 13, 14 or 15 nucleoside units, such as DNA units or other nuclease recruiting nucleosides such as alpha-L-LNA or a mixture of DNA and nuclease recruiting nucleosides.
• In a further specific embodiment, the oligonucleotide is a gapmer wherein each of regions F and F′ region consists of two LNA units each, and region G consists of 10, 11, 12, 13, 14 or 15 nucleoside units, preferably DNA units. Specific gapmer designs of this nature include 2-10-2, 2-11-2, 2-12-2, 2-13-2, 2-14-2 and 2-15-2.
• In a further specific embodiment, the oligonucleotide is a gapmer wherein each of regions F and F′ independently consists of three LNA units, and region G consists of 10, 11, 12, 13, 14 or 15 nucleoside units, preferably DNA units. Specific gapmer designs of this nature include 3-10-3, 3-11-3, 3-12-3, 3-13-3, 3-14-3 and 3-15-3.
• In a further specific embodiment, the oligonucleotide is a gapmer wherein each of regions F and F′ consists of four LNA units each, and region G consists of 10, 11, 12, 13, 14 or 15 nucleoside units, preferably DNA units. Specific gapmer designs of this nature include 4-10-4, 4-11-4, 4-12-4, 4-13-4, 4-14-4 and 4-15-4.
• Specific gapmer designs of this nature include F-G-F′ designs selected from a group consisting of a gap with 10 nucleosides and independently 1 to 4 modified nucleosides in the wings including 1-10-1, 2-10-1, 1-10-2, 1-10-3, 3-10-1, 1-10-4, 4-10-1, 2-10-2, 2-10-3, 3-10-2, 2-10-4, 4-10-2, 3-10-3, 3-10-4, 4-10-3 and 4-10-4 gapmers.
• Specific gapmer designs of this nature include F-G-F′ designs selected from a group consisting of a gap with 11 nucleosides and independently 1 to 4 modified nucleosides in the wings including, 1-11-1, 2-11-1, 1-11-2, 1-11-3, 3-11-1, 1-11-4, 4-11-1, 2-11-2, 2-11-3, 3-11-2, 2-11-4, 4-11-2, 3-11-3, 3-11-4, 4-11-3 and 4-11-4 gapmers.
• Specific gapmer designs of this nature include F-G-F′ designs selected from a group consisting of a gap with 12 nucleosides including, 1-12-1, 2-12-1, 1-12-2, 1-12-3, 3-12-1, 1-12-4, 4-12-1, 2-12-2, 2-12-3, 3-12-2, 2-12-4, 4-12-2, 3-12-3, 3-12-4, 4-12-3 and 4-12-4 gapmers.
• Specific gapmer designs of this nature include F-G-F′ designs selected from a group consisting of a gap with 13 nucleosides and independently 1 to 4 modified nucleosides in the wings including 1-13-1, 1-13-2, 1-13-3, 3-13-1, 1-13-4, 4-13-1, 2-13-1, 2-13-2, 2-13-3, 3-13-2, 2-13-4, 4-13-2, 3-13-3, 3-13-4, 4-13-3, and 4-13-4 gapmers.
• Specific gapmer designs of this nature include F-G-F′ designs selected from a group consisting of a gap with 14 nucleosides and independently 1 to 4 modified nucleosides in the wings including 1-14-1, 1-14-2, 2-14-1, 1-14-3, 3-14-1, 1-14-4, 4-14-1, 2-14-2, 2-14-3, 3-14-2 2-14-4, 4-14-2, 3-14-3, 3-14-4 and 4-14-3 gapmers.
• Specific gapmer designs of this nature include F-G-F′ designs selected from a group consisting of a gap with 15 nucleosides and independently 1 to 4 modified nucleosides in the wings including 1-15-1, 1-15-2, 2-15-1, 1-15-3, 3-15-1, 1-15-4, 4-15-1, 2-15-2, 2-15-3, 3-15-2 2-15-4, 4-15-2, 3-15-3, 3-15-4 and 4-15-3 gapmers.
• Specific gapmer designs of this nature include F-G-F′ designs selected from a group consisting of a gap with 16 nucleosides and independently 1 to 4 modified nucleosides in the wings including 1-16-1, 1-16-2, 2-16-1, 1-15-3, 3-16-1, 1-16-4, 4-16-1, 2-16-2, 2-16-3, 3-16-2 2-16-4, 4-16-2, 3-16-3, 3-16-4 and 4-16-3 gapmers.
• In some embodiments the F-G-F′ design is selected from 2-10-4, 3-10-3 and 4-10-2.
• In some embodiments the F-G-F′ design is selected from 2-11-4, 3-11-2, 3-11-3 and 4-11-2.
• In some embodiments the F-G-F′ design is selected from 2-12-2, 2-12-3, 2-12-4, 3-12-2, 3-12-3, and 4-12-2.
• In some embodiments the F-G-F′ design is selected from 2-13-2, 2-13-3, 2-13-4, 3-13-3 and 4-13-2.
• In some embodiments the F-G-F′ design is selected from 2-14-2, 2-14-4, 3-14-3 and 4-14-2.
• In some embodiments the F-G-F′ design is selected from 2-15-2 and 2-16-2.
• In some embodiments the F-G-F′ design is selected from the designs indicated in table 3.
• In all instances the F-G-F′ design may further include region D and/or D′, which may have 1, 2 or 3 nucleoside units, such as DNA units. Preferably, the nucleosides in region F and F′ are modified nucleosides, while nucleotides in region G are preferably unmodified nucleosides.
• In each design, the preferred modified nucleoside is LNA.
• In another embodiment all the internucleoside linkages in the gap in a gapmer are phosphorothioate and/or boranophosphate linkages. In another embodiment all the internucleoside linkages in the flanks (F and F′ region) in a gapmer are phosphorothioate and/or boranophosphate linkages. In another preferred embodiment all the internucleoside linkages in the D and D′ region in a gapmer are phosphodiester linkages.
• For specific gapmers as disclosed herein, when the cytosine (C) residues are annotated as 5-methyl-cytosine, in various embodiments, one or more of the C's present in the oligonucleotide may be unmodified C residues.
• Further gapmer designs are disclosed in WO2004/046160, WO2007/146511 and incorporated by reference.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds in table 3.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 4_1 to 150_2.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 4_1 to 678_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 4_1 to 818_1 (see oligonucleotide sequences listed in table 3 in the Examples section).
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 155_1 or 165_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 169_52, 169_50 or 169_56.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 172_1, 272_1, 572_7, 572_6 or 572_5.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 175_1.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 178_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 573_8, 186_1 or 187_1.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 186_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 200_1, 204_1, 206_1, 35_2 or 209_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 585_1, 585_8, 586_9, 586_5, 586_8, 586_4 or 586_6.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 233_1.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 237_8 or 590_13.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 220_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 591_1, 592_2, 592_4 or 241_9.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 597_4, 598_4, 39_1 or 602_1.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 39_1.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 611_7.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 271_1 or 278_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 616_4, 621_2, 621_1, 622_3, 622_5, 622_4, 6243, 624_5, 287_1, 625_6, 626_7, 626_8, 626_9, 48_1, 631_6, 631_1, 303_1, 304_6 or 304_10.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 636_8.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 638_8, 639_5, 331_1 or 640_4.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 359_1, 361_1, 361_5, 362_1 or 641_5.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 378_1, 379_1, 399_1.
• For certain embodiments of the invention, the oligonucleotide is selected from the group of oligonucleotide compounds with CMP-ID-NO: 403_1, 405_1, 642_12, 642_13, 644_3 or 646_16.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 85_1 or 425_5.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 116_1.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 123_1 or 124_1.
• For certain embodiments of the invention, the oligonucleotide is an oligonucleotide compound with CMP-ID-NO: 126_2.
Method of Manufacture
• In a further aspect, the invention provides methods for manufacturing the oligonucleotides of the invention comprising reacting nucleotide units and thereby forming covalently linked contiguous nucleotide units comprised in the oligonucleotide. Preferably, the method uses phophoramidite chemistry (see for example Caruthers et al, 1987, Methods in Enzymology vol. 154, pages 287-313). In a further embodiment the method further comprises reacting the contiguous nucleotide sequence with a conjugating moiety (ligand). In a further aspect a method is provided for manufacturing the composition of the invention, comprising mixing the oligonucleotide or conjugated oligonucleotide of the invention with a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.
Pharmaceutical Composition
• In a further aspect, the invention provides pharmaceutical compositions comprising any of the aforementioned oligonucleotides and/or oligonucleotide conjugates and a pharmaceutically acceptable diluent, carrier, salt and/or adjuvant. A pharmaceutically acceptable diluent includes phosphate-buffered saline (PBS) and pharmaceutically acceptable salts include, but are not limited to, sodium and potassium salts.
• WO 2007/031091 provides suitable and preferred examples of pharmaceutically acceptable diluents, carriers and adjuvants (hereby incorporated by reference). Suitable dosages, formulations, administration routes, compositions, dosage forms, combinations with other therapeutic agents, pro-drug formulations are also provided in WO2007/031091.
• Oligonucleotides or oligonucleotide conjugates of the invention may be mixed with pharmaceutically acceptable active or inert substances for the preparation of pharmaceutical compositions or formulations. Compositions and methods for the formulation of pharmaceutical compositions are dependent upon a number of criteria, including, but not limited to, route of administration, extent of disease, or dose to be administered.
• In some embodiments, the oligonucleotide or oligonucleotide conjugate of the invention is a prodrug. In particular with respect to oligonucleotide conjugates the conjugate moiety is cleaved of the oligonucleotide once the prodrug is delivered to the site of action, e.g. the target cell.
Applications
• The oligonucleotides of the invention may be utilized as research reagents for, for example, therapeutics and prophylaxis.
• In research, such oligonucleotides may be used to specifically modulate the synthesis of UBE3A protein in cells (e.g. in vitro cell cultures) and experimental animals thereby facilitating functional analysis of the target or an appraisal of its usefulness as a target for therapeutic intervention. The target modulation is achieved by degrading or inhibiting a modulator of the gene or mRNA producing the protein.
• For therapeutics, an animal or a human, suspected of having a disease or disorder, which can be treated by modulating the expression of UBE3A.
• The invention provides methods for treating or preventing a disease, comprising administering a therapeutically or prophylactically effective amount of an oligonucleotide, an oligonucleotide conjugate or a pharmaceutical composition of the invention to a subject suffering from or susceptible to the disease.
• The invention also relates to an oligonucleotide, a composition or a conjugate as defined herein for use as a medicament.
• The oligonucleotide, oligonucleotide conjugate or a pharmaceutical composition according to the invention is typically administered in an effective amount.
• The invention also provides for the use of the oligonucleotide or oligonucleotide conjugate of the invention as described for the manufacture of a medicament for the treatment of a disorder as referred to herein, or for a method of the treatment of as a disorder as referred to herein.
• The disease or disorder, as referred to herein, is associated with expression of UBE3A. In some embodiments the disease or disorder may be associated with a mutation in the maternal UBE3A gene. In some embodiments, the target nucleic acid is a regulator of the paternal UBE3A gene.
• The methods of the invention are preferably employed for treatment or prophylaxis against diseases caused by abnormal levels and/or activity of UBE3A. The disease may in particular be caused by reduced levels and/or activity of UBE3A protein.
• The invention further relates to use of an oligonucleotide, oligonucleotide conjugate or a pharmaceutical composition as defined herein for the manufacture of a medicament for the treatment of abnormal levels and/or activity of UBE3A, in particular low levels and/or activity of UBE3A.
• In one embodiment, the invention relates to oligonucleotides, oligonucleotide conjugates or pharmaceutical compositions for use in the treatment of Angelman syndrome.
Administration
• The oligonucleotides or pharmaceutical compositions of the present invention may be administered topical (such as, to the skin, inhalation, ophthalmic or otic) or enteral (such as, orally or through the gastrointestinal tract) or parenteral (such as, intravenous, subcutaneous, intra-muscular, intracerebral, intracerebroventricular or intrathecal).
• In a preferred embodiment the oligonucleotide or pharmaceutical compositions of the present invention are administered by a parenteral route including intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion, intrathecal or intracranial, e.g., intracerebral or intraventricular, administration. In one embodiment the active oligonucleotide or oligonucleotide conjugate is administered intracerebral or intracerebroventricular. In another embodiment the active oligonucleotide or oligonucleotide conjugate is administered intrathecal.
• The invention also provides for the use of the oligonucleotide or oligonucleotide conjugate of the invention as described for the manufacture of a medicament wherein the medicament is in a dosage form for intrathecal administration.
• The invention also provides for the use of the oligonucleotide or oligonucleotide conjugate of the invention as described for the manufacture of a medicament wherein the medicament is in a dosage form for intracerebral or intraventricular administration.
• The invention also provides for the use of the oligonucleotide or oligonucleotide conjugate of the invention as described for the manufacture of a medicament wherein the medicament is in a dosage form for intracerebroventricular administration.
Combination Therapies
• In some embodiments the oligonucleotide, oligonucleotide conjugate or pharmaceutical composition of the invention is for use in a combination treatment with another therapeutic agent. The therapeutic agent can for example be anticonvulsant medication.
EMBODIMENTS
• The following embodiments of the present invention may be used in combination with any other embodiments described herein.
• 1. An antisense oligonucleotide which comprises or consists of a contiguous nucleotide sequence of 10 to 30 nucleotides in length capable of inducing human paternal UBE3A expression, in particular in a neuronal cell.
• 2. The oligonucleotide of embodiment 1, wherein the contiguous nucleotide sequence is at least 95% complementarity to the part of human SNHG14 long non-coding RNA which is downstream of SNORD109B corresponding to position 25278410 to 25419462 on chromosome 15.
• 3. The oligonucleotide of embodiment 1 or 2, wherein the oligonucleotide is capable of hybridizing to a target nucleic acid of SEQ ID NO: 1 with a ΔG° below −10 kcal.
• 4. The oligonucleotide of embodiment 1-3, wherein the contiguous nucleotide sequence is at least 95%, such as 98%, such as 100% complementarity to region of the target nucleic acid of SEQ ID NO: 1 and/or 2.
• 5. The oligonucleotide of embodiment 1-3, wherein the contiguous nucleotide sequence is 100% complementary to a region of the target nucleic acid of position 1 to 55318 of SEQ ID NO: 1.
• 6. The oligonucleotide of embodiment 1-4, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid, wherein the subsequence is selected from the group consisting of the regions indicated in table 1 or 2.
• 7. The oligonucleotide of embodiment 1-4, wherein the contiguous nucleotide sequence is at least 98% complementarity to the part of human SNHG14 long non-coding RNA which is antisense to the UBE3A pre-mRNA.
• 8. The oligonucleotide of embodiments 1-4 or 7, wherein the oligonucleotide is capable of hybridizing to a target nucleic acid corresponding to position 55319 to 141053 of SEQ ID NO: 1, with a ΔG° below −10 kcal.
• 9. The oligonucleotide of embodiments 1-4 or 7-8, wherein the contiguous nucleotide sequence is 100% complementary to a target nucleic acid of position 55319 to 141053 of SEQ ID NO: 1.
• 10. The oligonucleotide of embodiment 1-8, wherein the target nucleic acid is RNA.
• 11. The oligonucleotide of embodiment 10, wherein the RNA is a long non-coding RNA.
• 12. The oligonucleotide of embodiment 1-11, wherein the contiguous nucleotide sequence comprises or consists of at least 10 contiguous nucleotides, particularly 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 contiguous nucleotides.
• 13. The oligonucleotide of embodiment 1-12, wherein the contiguous nucleotide sequence comprises or consists of from 12 to 22 nucleotides.
• 14. The oligonucleotide of embodiment 13, wherein the contiguous nucleotide sequence comprises or consists of from 15-20 nucleotides.
• 15. The oligonucleotide of embodiment 1-14, wherein the oligonucleotide comprises or consists of 10 to 35 nucleotides in length.
• 16. The oligonucleotide of embodiment 15, wherein the oligonucleotide comprises or consists of 15 to 24 nucleotides in length.
• 17. The oligonucleotide of embodiment 15 or 17, wherein the oligonucleotide comprises or consists of 17 to 22 nucleotides in length.
• 18. The oligonucleotide of embodiment 1-17, wherein the oligonucleotide or contiguous nucleotide sequence is single stranded.
• 19. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid, selected from the group consisting of the regions indicated in table 1 or 2.
• 20. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid selected from the group consisting of position 1589-10889, 46089-53989 and 60789-62489 of SEQ ID NO: 1.
• 21. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 5218-5240 of SEQ ID NO: 1.
• 22. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 5782-5803 of SEQ ID NO: 1.
• 23. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 8113-8139 of SEQ ID NO: 1.
• 24. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions: 9200-9250 of SEQ ID NO: 1.
• 25. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions: 11505-11555 of SEQ ID NO: 1.
• 26. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 13223-13242 of SEQ ID NO: 1.
• 27. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 15100-15150 of SEQ ID NO: 1.
• 28. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 15113-15180 of SEQ ID NO: 1.
• 29. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 29635-29705 of SEQ ID NO: 1.
• 30. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 30590-30740 of SEQ ID NO: 1.
• 31. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 39800-39855 of SEQ ID NO: 1.
• 32. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 44435-44460 of SEQ ID NO: 1.
• 33. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 45245-45270 of SEQ ID NO: 1
• 34. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid to positions 46380-46430 of SEQ ID NO: 1.
• 35. The oligonucleotide of embodiment 1-18, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid corresponding to positions 68915-68940 of SEQ ID NO: 1.
• 36. The oligonucleotide of embodiment 1-35, wherein the oligonucleotide is neither siRNA nor self-complementary.
• 37. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 1819, 20, 21, 22, 23, 23, 24, 25, 26, 26, 27, 28, 29, 30, 31, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 44, 45, 45, 46, 47, 48, 49, 50, 51, 52, 53, 53, 54, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 79, 80, 81, 8283, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 95, 96, 96, 96, 97, 98, 99, 100, 101, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817 and 818.
• 38. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 166, 167, 167 or 169 (see motif sequences listed in table 3 in the Examples section).
• 39. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 570, 571, 572, 679, 680, 681, 682 and 683 (see motif sequences listed in table 3 in the Examples section).
• 40. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 570, 571, 572, 679, 680, 681, 682 and 683 (see motif sequences listed in table 3 in the Examples section).
• 41. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 35, 199 to 210 or SEQ ID NO: 582 to 584 (see motif sequences listed in table 3 in the Examples section).
• 42. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 236, 237, 238, 239, 240 and 590 (see motif sequences listed in table 3 in the Examples section).
• 43. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 221 to 225 or SEQ ID NO: 585 to 589 (see motif sequences listed in table 3 in the Examples section).
• 44. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 241 or 591 (see motif sequences listed in table 3 in the Examples section).
• 45. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 46-48, 285 to 305 or SEQ ID NO: 613 to 632 or SEQ ID NO: 721 to 807 (see motif sequences listed in table 3 in the Examples section).
• 46. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 331, 332, 638, 639, 640, 808, 809, 810, 811, 812, 813, 814 and 815 (see motif sequences listed in table 3 in the Examples section).
• 47. The oligonucleotide of embodiment 1-36, wherein the contiguous nucleotide sequence comprises or consists of a sequence selected from the group consisting of SEQ ID NO: 409 to 411 or SEQ ID NO: 642 to 646 or SEQ ID NO: 816 to 818 (see motif sequences listed in table 3 in the Examples section).
• 48. The oligonucleotide of embodiment 1-47, wherein the contiguous nucleotide sequence has zero to three mismatches compared to the target nucleic acid it is complementary to.
• 49. The oligonucleotide of embodiment 48, wherein the contiguous nucleotide sequence has one mismatch compared to the target nucleic acid.
• 50. The oligonucleotide of embodiment 48, wherein the contiguous nucleotide sequence has two mismatches compared to the target nucleic acid.
• 51. The oligonucleotide of embodiment 48, wherein the contiguous nucleotide sequence is fully complementary to the target nucleic acid sequence.
• 52. The oligonucleotide of embodiment 1-51, comprising one or more modified nucleosides.
• 53. The oligonucleotide of embodiment 52, wherein the one or more modified nucleoside is a high-affinity modified nucleosides.
• 54. The oligonucleotide of embodiment 52 or 53, wherein the one or more modified nucleoside is a 2′ sugar modified nucleoside.
• 55. The oligonucleotide of embodiment 54, wherein the one or more 2′ sugar modified nucleoside is independently selected from the group consisting of 2′-O-alkyl-RNA, 2′-O-methyl-RNA, 2′-alkoxy-RNA, 2′-O-methoxyethyl-RNA, 2′-amino-DNA, 2′-fluoro-DNA, 2′-fluoro-ANA and LNA nucleosides.
• 56. The oligonucleotide of embodiment 54, wherein the one or more modified nucleoside is a LNA nucleoside.
• 57. The oligonucleotide of embodiment 56, wherein the modified LNA nucleoside is oxy-LNA.
• 58. The oligonucleotide of embodiment 57, wherein the modified nucleoside is beta-D-oxy-LNA.
• 59. The oligonucleotide of embodiment 57, wherein the modified nucleoside is alpha-L-oxy-LNA
• 60. The oligonucleotide of embodiment 56, wherein the modified nucleoside is thio-LNA.
• 61. The oligonucleotide of embodiment 56, wherein the modified nucleoside is amino-LNA.
• 62. The oligonucleotide of embodiment 56, wherein the modified nucleoside is cET.
• 63. The oligonucleotide of embodiment 56, wherein the modified nucleoside is ENA.
• 64. The oligonucleotide of embodiment 56, wherein the modified LNA nucleoside is selected from beta-D-oxy-LNA, alpha-L-oxy-LNA, beta-D-amino-LNA, alpha-L-amino-LNA, beta-D-thio-LNA, alpha-L-thio-LNA, (S)cET, (R)cET beta-D-ENA and alpha-L-ENA.
• 65. The oligonucleotide of any one of embodiments 1-64, wherein the oligonucleotide comprises at least one modified internucleoside linkage.
• 66. The oligonucleotide of embodiment 65, wherein the modified internucleoside linkage is nuclease resistant.
• 67. The oligonucleotide of embodiment 65 or 66, wherein at least 50% of the internucleoside linkages within the contiguous nucleotide sequence are phosphorothioate internucleoside linkages or boranophosphate internucleoside linkages.
• 68. The oligonucleotide of embodiment 65 or 66, wherein all the internucleoside linkages within the contiguous nucleotide sequence are phosphorothioate internucleoside linkages.
• 69. The oligonucleotide of embodiment 1-68, wherein the oligonucleotide is capable of recruiting RNase H.
• 70. The oligonucleotide of embodiment 69, wherein the oligonucleotide is a gapmer.
• 71. The oligonucleotide of embodiment 69 or 70, wherein the oligonucleotide is a gapmer of formula 5′-F-G-F′-3′, where region F and F′ independently comprise or consist of 1-7 modified nucleosides and G is a region between 6 and 16 nucleosides which are capable of recruiting RNaseH.
• 72. The oligonucleotide of embodiment 71, wherein the modified nucleoside is a 2′ sugar modified nucleoside independently selected from the group consisting of 2′-O-alkyl-RNA, 2′-O-methyl-RNA, 2′-alkoxy-RNA, 2′-O-methoxyethyl-RNA, 2′-amino-DNA, 2′-fluoro-DNA, arabino nucleic acid (ANA), 2′-fluoro-ANA and LNA nucleosides.
• 73. The oligonucleotide of embodiment 71 or 72, wherein one or more of the modified nucleosides in region F and F′ is a LNA nucleoside.
• 74. The oligonucleotide of embodiment 73, wherein all the modified nucleosides in region F and F′ are LNA nucleosides.
• 75. The oligonucleotide of embodiment 74, wherein region F and F′ consist of LNA nucleosides.
• 76. The oligonucleotide of embodiment 73-75, wherein all the modified nucleosides in region F and F′ are oxy-LNA nucleosides.
• 77. The oligonucleotide of embodiment 73, wherein at least one of region F or F′ further comprises at least one 2′ substituted modified nucleoside independently selected from the group consisting of 2′-O-alkyl-RNA, 2′-O-methyl-RNA, 2′-alkoxy-RNA, 2′-O-methoxyethyl-RNA, 2′-amino-DNA and 2′-fluoro-DNA.
• 78. The oligonucleotide of embodiment 73-77, wherein the RNaseH recruiting nucleosides in region G are independently selected from DNA, alpha-L-LNA, C4′ alkylated DNA, ANA and 2′F-ANA and UNA.
• 79. The oligonucleotide of embodiment 78, wherein the nucleosides in region G is DNA and/or alpha-L-LNA nucleosides.
• 80. The oligonucleotide of embodiment 78 or 79, wherein region G consists of at least 75% DNA nucleosides.
• 81. The oligonucleotide of embodiment 1-80, wherein the oligonucleotide is capable of increasing the expression of UBE3A by at least 30% compared to a control.
• 82. The oligonucleotide of embodiment 1-81, wherein the level of the SNHG14 transcript downstream of SNORD109B is reduced by at least 20% compared to a control.
• 83. The oligonucleotide of embodiment 1-82, wherein the expression of SNORD115 is not significantly affected compared to a control.
• 84. The oligonucleotide of embodiment 1-83, wherein the oligonucleotide is selected from CMP ID NO: 4_1 to 678_1.
• 85. The oligonucleotide of embodiment 1-83, wherein the oligonucleotide is selected from the group consisting of CMP ID NO: 4_1, 4_2, 5_1, 5_2, 6_1, 6_2, 7_1, 7_2, 8_1, 9_1, 10_1, 11_1, 11_2, 12_1, 12_2, 13_1, 13_2, 14_1, 15_1, 16_1, 17_1, 17_2, 18_1, 18_2, 19_1, 19_2, 20_1, 21_1, 22_1, 23_1, 23_2, 24_1, 25_1, 26_1, 26_2, 27_1, 28_1, 28_2, 29_1, 29_2, 30_1, 31_1, 31_2, 32_1, 33_1, 34_1, 34_2, 34_3, 34_4, 34_5, 34_6, 34_7, 35_1, 35_2, 36_1, 37_1, 38_1, 38_2, 38_3, 38_4, 38_5, 38_6, 39_1, 39_2, 39_3, 39_4, 39_5, 40_1, 40_2, 40_3, 40_4, 40_5, 40_6, 40_7, 40_8, 41_1, 42_1, 43_1, 44_1, 44_2, 45_1, 45_2, 46_1, 47_1, 48_1, 48_2, 48_3, 48_4, 48_5, 48_6, 48_7, 49_1, 50_1, 51_1, 52_1, 53_1, 53_2, 54_1, 54_2, 54_3, 55_1, 55_2, 56_1, 57_1, 58_1, 58_2, 58_3, 59_1, 59_2, 60_1, 60_2, 60_3, 61_1, 62_1, 63_1, 64_1, 64_2, 65_1, 66_1, 67_1, 68_1, 69_1, 69_2, 69_3, 70_1, 70_2, 70_3, 71_1, 72_1, 72_2, 73_1, 73_2, 73_3, 74_1, 74_2, 75_1, 75_2, 76_1, 77_1, 77_2, 77_3, 78_1, 79_1, 79_2, 79_3, 80_1, 80_2, 80_3, 81_1, 82_1, 82_2, 83_1, 83_2, 84_1, 84_2, 85_1, 85_2, 86_1, 87_1, 88_1, 88_2, 89_1, 90_1, 91_1, 92_1, 93_1, 94_1, 95_1, 95_2, 96_1, 96_2, 96_3, 97_1, 97_2, 97_3, 97_4, 98_1, 98_2, 98_3, 99_1, 99_2, 99_3, 99_4, 100_1, 100_2, 100_3, 101_1, 101_2, 101_3, 101_4, 102_1, 102_2, 102_3, 102_4, 103_1, 103_2, 103_3, 103_4, 104_1, 104_2, 104_3, 105_1, 105_2, 105_3, 105_4, 106_1, 106_2, 106_3, 106_4, 107_1, 107_2, 107_3, 107_4, 108_1, 108_2, 108_3, 108_4, 109_1, 109_2, 109_3, 109_4, 110_1, 110_2, 111_1, 111_2, 111_3, 112_1, 112_2, 113_1, 114_1, 115_1, 116_1, 117_1, 118_1, 119_1, 120_1, 120_2, 121_1, 122_1, 123_1, 124_1, 125_1, 126_1, 126_2, 127_1, 128_1, 128_2, 128_3, 128_4, 129_1, 129_2, 130_1, 131_1, 132_1, 132_2, 132_3, 133_1, 133_2, 133_3, 133_4, 134_1, 134_2, 135_1, 135_2, 136_1, 137_1, 138_1, 139_1, 140_1, 141_1, 142_1, 143_1, 144_1, 145_1, 145_2, 146_1, 146_2, 147_1, 148_1, 149_1, 150_1, 150_2, 151_1, 152_1, 153_1, 154_1, 155_1, 156_1, 157_1, 158_1, 159_1, 160_1, 161_1, 162_1, 163_1, 164_1, 165_1, 166_1, 167_1, 168_1, 169_1, 169_10, 169_11, 169_12, 169_13, 169_14, 169_15, 169_16, 169_17, 169_18, 169_19, 169_2, 169_20, 169_21, 169_22, 169_23, 169_24, 169_25, 169_26, 169_27, 169_28, 169_29, 169_3, 169_30, 169_31, 169_32, 169_33, 169_34, 169_35, 169_36, 169_37, 169_38, 169_39, 169_4, 169_40, 169_41, 169_42, 169_43, 169_44, 169_45, 169_46, 169_47, 169_48, 169_49, 169_5, 169_50, 169_51, 169_52, 169_53, 169_54, 169_55, 169_56, 169_57, 169_6, 169_7, 169_8, 169_9, 169_58, 169_59, 169_60, 169_61, 169_62, 170_1, 171_1, 172_1, 173_1, 174_1, 175_1, 176_1, 177_1, 178_1, 179_1, 180_1, 181_1, 182_1, 183_1, 184_1, 185_1, 186_1, 187_1, 188_1, 189_1, 190_1, 191_1, 192_1, 193_1, 194_1, 195_1, 196_1, 197_1, 198_1, 199_1, 200_1, 201_1, 202_1, 203_1, 204_1, 205_1, 206_1, 207_1, 208_1, 208_2, 208_3, 208_4, 208_5, 208_6, 208_7, 209_1, 209_10, 209_2, 209_3, 209_4, 209_5, 209_6, 209_7, 209_8, 209_9, 210_1, 211_1, 212_1, 213_1, 214_1, 215_1, 216_1, 217_1, 218_1, 219_1, 220_1, 221_1, 222_1, 223_1, 224_1, 225_1, 226_1, 227_1, 228_1, 229_1, 230_1, 231_1, 232_1, 233_1, 234_1, 235_1, 236_1, 236_10, 236_11, 236_12, 236_13, 236_14, 236_15, 236_16, 236_2, 236_3, 236_4, 236_5, 236_6, 236_7, 236_8, 236_9, 236_17, 236_18, 236_19, 236_20, 236_21, 237_1, 237_10, 237_11, 237_12, 237_13, 237_14, 237_15, 237_16, 237_2, 237_3, 237_4, 237_5, 237_6, 237_7, 237_8, 237_9, 237_17, 237_18, 237_19, 237_20, 237_21, 238_1, 239_1, 239_10, 239_11, 239_12, 239_13, 239_14, 239_15, 239_16, 239_2, 239_3, 239_4, 239_5, 239_6, 239_7, 239_8, 239_9, 239_17, 239_18, 239_19, 239_20, 239_21, 240_1, 241_1, 241_10, 241_2, 241_3, 241_4, 241_5, 241_6, 241_7, 241_8, 241_9, 241_11, 241_12, 241_13, 241_14, 241_15, 242_1, 243_1, 244_1, 244_2, 244_3, 244_4, 244_5, 245_1, 246_1, 247_1, 248_1, 249_1, 250_1, 251_1, 252_1, 253_1, 254_1, 255_1, 256_1, 257_1, 258_1, 259_1, 260_1, 261_1, 262_1, 263_1, 264_1, 265_1, 266_1, 267_1, 268_1, 269_1, 270_1, 271_1, 272_1, 273_1, 274_1, 275_1, 276_1, 277_1, 278_1, 279_1, 280_1, 281_1, 282_1, 283_1, 284_1, 285_1, 285_2, 285_3, 285_4, 285_5, 285_6, 285_7, 285_8, 285_9, 285_10, 285_11, 286_1, 287_1, 288_1, 289_1, 290_1, 291_1, 292_1, 293_1, 294_1, 295_1, 296_1, 297_1, 298_1, 299_1, 300_1, 301_1, 302_1, 303_1, 304_1, 304_10, 304_2, 304_3, 304_4, 304_5, 304_6, 304_7, 304_8, 304_9, 304_11, 304_12, 304_13, 304_14, 304_15, 305_1, 306_1, 307_1, 308_1, 309_1, 310_1, 311_1, 312_1, 313_1, 314_1, 315_1, 316_1, 317_1, 318_1, 319_1, 320_1, 321_1, 322_1, 323_1, 324_1, 325_1, 326_1, 327_1, 328_1, 329_1, 330_1, 331_1, 332_1, 333_1, 334_1, 335_1, 336_1, 337_1, 338_1, 339_1, 340_1, 341_1, 342_1, 343_1, 344_1, 345_1, 346_1, 347_1, 348_1, 349_1, 350_1, 351_1, 352_1, 353_1, 354_1, 355_1, 356_1, 357_1, 358_1, 359_1, 360_1, 361_1, 361_10, 361_2, 361_3, 361_4, 361_5, 361_6, 361_7, 361_8, 361_9, 362_1, 362_10, 362_2, 362_3, 362_4, 362_5, 362_6, 362_7, 362_8, 362_9, 363_1, 364_1, 365_1, 366_1, 367_1, 368_1, 369_1, 370_1, 371_1, 372_1, 373_1, 374_1, 375_1, 376_1, 377_1, 378_1, 379_1, 380_1, 381_1, 382_1, 383_1, 384_1, 385_1, 386_1, 387_1, 388_1, 389_1, 390_1, 391_1, 392_1, 393_1, 394_1, 395_1, 396_1, 397_1, 398_1, 399_1, 400_1, 401_1, 402_1, 403_1, 404_1, 405_1, 406_1, 407_1, 408_1, 409_1, 410_1, 411_1, 412_1, 413_1, 414_1, 415_1, 416_1, 417_1, 418_1, 419_1, 420_1, 421_1, 422_1, 423_1, 424_1, 425_1, 425_10, 425_2, 425_3, 425_4, 425_5, 425_6, 425_7, 425_8, 425_9, 426_1, 427_1, 428_1, 429_1, 430_1, 431_1, 432_1, 433_1, 434_1, 435_1, 436_1, 437_1, 438_1, 439_1, 440_1, 441_1, 442_1, 443_1, 444_1, 445_1, 446_1, 447_1, 448_1, 449_1, 450_1, 451_1, 452_1, 453_1, 454_1, 455_1, 456_1, 457_1, 458_1, 459_1, 460_1, 461_1, 462_1, 463_1, 464_1, 465_1, 466_1, 467_1, 468_1, 469_1, 470_1, 471_1, 472_1, 473_1, 474_1, 475_1, 476_1, 477_1, 478_1, 479_1, 480_1, 481_1, 482_1, 483_1, 484_1, 485_1, 486_1, 487_1, 488_1, 489_1, 490_1, 491_1, 492_1, 493_1, 494_1, 495_1, 496_1, 497_1, 498_1, 499_1, 500_1, 501_1, 502_1, 503_1, 504_1, 505_1, 506_1, 507_1, 508_1, 509_1, 510_1, 511_1, 512_1, 513_1, 514_1, 515_1, 516_1, 517_1, 518_1, 519_1, 520_1, 521_1, 522_1, 523_1, 524_1, 525_1, 526_1, 527_1, 528_1, 529_1, 530_1, 531_1, 532_1, 533_1, 534_1, 535_1, 536_1, 537_1, 538_1, 539_1, 540_1, 541_1, 542_1, 543_1, 544_1, 545_1, 546_1, 547_1, 548_1, 549_1, 550_1, 551_1, 552_1, 553_1, 554_1, 555_1, 556_1, 557_1, 558_1, 559_1, 560_1, 561_1, 562_1, 563_1, 564_1, 565_1, 566_1, 567_1, 568_1, 569_1, 570_1, 570_2, 570_3, 570_4, 570_5, 570_6, 570_7, 570_8, 570_9, 570_10, 570_11, 570_12, 570_13, 570_14, 571_1, 571_2, 571_3, 571_4, 571_5, 571_6, 571_7, 571_8, 571_9, 571_10, 571_11, 571_12, 571_13, 571_14, 572_1, 572_2, 572_3, 572_4, 572_5, 572_6, 572_7, 572_8, 572_9, 572_10, 572_11, 572_12, 572_13, 572_14, 573_1, 573_2, 573_3, 573_4, 573_5, 573_6, 573_7, 573_8, 573_9, 573_10, 573_11, 573_12, 573_13, 573_14, 574_1, 574_2, 574_3, 574_4, 574_5, 574_6, 574_7, 574_8, 574_9, 574_10, 574_11, 574_12, 574_13, 574_14, 575_1, 575_2, 575_3, 575_4, 575_5, 575_6, 575_7, 575_8, 575_9, 575_10, 575_11, 575_12, 575_13, 575_14, 576_1, 576_2, 576_3, 576_4, 576_5, 576_6, 576_7, 576_8, 576_9, 576_10, 576_11, 576_12, 576_13, 576_14, 577_1, 577_2, 577_3, 577_4, 577_5, 577_6, 577_7, 577_8, 577_9, 577_10, 577_11, 577_12, 577_13, 577_14, 578_1, 578_2, 578_3, 578_4, 578_5, 578_6, 578_7, 578_8, 578_9, 579_1, 579_2, 579_3, 579_4, 579_5, 579_6, 579_7, 579_8, 579_9, 580_1, 580_2, 580_3, 580_4, 580_5, 580_6, 580_7, 580_8, 580_9, 581_1, 581_2, 581_3, 581_4, 581_5, 581_6, 581_7, 581_8, 581_9, 582_1, 582_2, 582_3, 582_4, 582_5, 582_6, 582_7, 582_8, 582_9, 583_1, 583_2, 583_3, 583_4, 583_5, 583_6, 583_7, 583_8, 583_9, 584_1, 584_2, 584_3, 584_4, 584_5, 584_6, 584_7, 584_8, 585_1, 585_2, 585_3, 585_4, 585_5, 585_6, 585_7, 585_8, 585_9, 585_10, 585_11, 585_12, 585_13, 585_14, 586_1, 586_2, 586_3, 586_4, 586_5, 586_6, 586_7, 586_8, 586_9, 586_10, 586_11, 586_12, 586_13, 586_14, 587_1, 587_2, 587_3, 587_4, 587_5, 587_6, 587_7, 587_8, 587_9, 587_10, 587_11, 587_12, 587_13, 587_14, 588_1, 588_2, 588_3, 588_4, 588_5, 588_6, 588_7, 588_8, 588_9, 588_10, 588_11, 588_12, 588_13, 588_14, 589_1, 589_2, 589_3, 589_4, 589_5, 589_6, 589_7, 589_8, 589_9, 589_10, 589_11, 589_12, 589_13, 589_14, 590_1, 590_10, 590_11, 590_12, 590_13, 590_14, 590_15, 590_2, 590_3, 590_4, 590_5, 590_6, 590_7, 590_8, 590_9, 590_16, 590_17, 590_18, 590_19, 590_20, 591_1, 591_2, 592_1, 592_2, 592_3, 592_4, 592_5, 592_6, 592_7, 592_8, 592_9, 592_10, 592_11, 592_12, 592_13, 592_14, 593_1, 593_2, 593_3, 593_4, 594_1, 594_2, 594_3, 594_4, 595_1, 595_2, 595_3, 595_4, 596_1, 596_2, 596_3, 596_4, 597_1, 597_2, 597_3, 597_4, 598_1, 598_2, 598_3, 598_4, 599_1, 599_2, 599_3, 599_4, 600_1, 600_2, 600_3, 600_4, 601_1, 601_2, 601_3, 601_4, 602_1, 602_2, 602_3, 602_4, 603_1, 603_2, 603_3, 603_4, 604_1, 604_2, 604_3, 604_4, 605_1, 605_2, 605_3, 605_4, 606_1, 606_2, 606_3, 606_4, 607_1, 607_2, 607_3, 607_4, 608_1, 608_2, 608_3, 608_4, 608_5, 608_6, 608_7, 608_8, 608_9, 609_1, 609_2, 609_3, 609_4, 609_5, 609_6, 609_7, 609_8, 609_9, 610_1, 610_2, 610_3, 610_4, 610_5, 610_6, 610_7, 610_8, 610_9, 611_1, 611_2, 611_3, 611_4, 611_5, 611_6, 611_7, 611_8, 611_9, 612_1, 612_2, 612_3, 612_4, 612_5, 612_6, 612_7, 612_8, 612_9, 613_1, 613_2, 613_3, 613_4, 613_5, 613_6, 613_7, 613_8, 613_9, 613_10, 614_1, 614_2, 614_3, 614_4, 614_5, 614_6, 614_7, 614_8, 614_9, 614_10, 615_1, 615_2, 615_3, 615_4, 615_5, 615_6, 615_7, 615_8, 615_9, 615_10, 616_1, 616_2, 616_3, 616_4, 616_5, 616_6, 616_7, 616_8, 616_9, 616_10, 617_1, 617_2, 617_3, 617_4, 617_5, 617_6, 617_7, 617_8, 617_9, 617_10, 618_1, 618_2, 618_3, 618_4, 618_5, 618_6, 618_7, 618_8, 618_9, 618_10, 619_1, 619_2, 619_3, 619_4, 619_5, 619_6, 619_7, 619_8, 619_9, 619_10, 620_1, 620_2, 620_3, 620_4, 620_5, 620_6, 620_7, 620_8, 620_9, 620_10, 621_1, 621_2, 621_3, 621_4, 621_5, 621_6, 621_7, 621_8, 621_9, 621_10, 621_11, 622_1, 622_2, 622_3, 622_4, 622_5, 622_6, 622_7, 622_8, 622_9, 622_10, 623_1, 623_2, 623_3, 623_4, 623_5, 623_6, 623_7, 623_8, 623_9, 623_10, 624_1, 624_2, 624_3, 624_4, 624_5, 624_6, 624_7, 624_8, 624_9, 624_10, 625_1, 625_2, 625_3, 625_4, 625_5, 625_6, 625_7, 625_8, 625_9, 625_10, 625_11, 625_12, 625_13, 625_14, 626_1, 626_2, 626_3, 626_4, 626_5, 626_6, 626_7, 626_8, 626_9, 626_10, 626_11, 626_12, 626_13, 626_14, 627_1, 627_2, 627_3, 627_4, 627_5, 627_6, 627_7, 627_8, 627_9, 627_10, 627_11, 627_12, 627_13, 627_14, 628_1, 628_2, 628_3, 628_4, 628_5, 628_6, 628_7, 628_8, 628_9, 628_10, 628_11, 628_12, 628_13, 628_14, 629_1, 629_10, 629_11, 629_2, 629_3, 629_4, 629_5, 629_6, 629_7, 629_8, 629_9, 629_12, 629_13, 629_14, 629_15, 629_16, 630_1, 630_2, 630_3, 631_1, 631_10, 631_2, 631_3, 631_4, 631_5, 631_6, 631_7, 631_8, 631_9, 631_11, 631_12, 631_13, 631_14, 631_15, 632_1, 632_2, 632_3, 632_4, 632_5, 632_6, 632_7, 632_8, 632_9, 632_10, 632_11, 632_12, 632_13, 632_14, 633_1, 633_2, 633_3, 633_4, 633_5, 633_6, 633_7, 633_8, 633_9, 634_1, 634_2, 634_3, 634_4, 634_5, 634_6, 634_7, 634_8, 634_9, 635_1, 635_2, 635_3, 635_4, 635_5, 635_6, 635_7, 635_8, 635_9, 636_1, 636_2, 636_3, 636_4, 636_5, 636_6, 636_7, 636_8, 636_9, 637_1, 637_2, 637_3, 637_4, 637_5, 637_6, 637_7, 637_8, 637_9, 638_1, 638_2, 638_3, 638_4, 638_5, 638_6, 638_7, 638_8, 638_9, 638_10, 638_11, 638_12, 638_13, 638_14, 639_1, 639_2, 639_3, 639_4, 639_5, 639_6, 639_7, 639_8, 639_9, 639_10, 639_11, 639_12, 639_13, 639_14, 640_1, 640_2, 640_3, 640_4, 640_5, 640_6, 640_7, 640_8, 640_9, 640_10, 640_11, 640_12, 640_13, 640_14, 641_1, 641_2, 641_3, 641_4, 641_5, 641_6, 641_7, 641_8, 641_9, 642_1, 642_10, 642_11, 642_12, 642_13, 642_14, 642_15, 642_16, 642_17, 642_2, 642_3, 642_4, 642_5, 642_6, 642_7, 642_8, 642_9, 642_18, 642_19, 642_20, 642_21, 642_22, 643_1, 644_1, 644_2, 644_3, 644_4, 644_5, 644_6, 645_1, 645_2, 645_3, 645_4, 645_5, 645_6, 645_7, 645_8, 645_9, 645_10, 646_1, 646_10, 646_11, 646_12, 646_13, 646_14, 646_15, 646_16, 646_17, 646_18, 646_19, 646_2, 646_3, 646_4, 646_5, 646_6, 646_7, 646_8, 646_9, 646_20, 646_21, 646_22, 646_23, 646_24, 647_1, 648_1, 649_1, 650_1, 651_1, 652_1, 653_1, 654_1, 655_1, 656_1, 657_1, 658_1, 659_1, 660_1, 661_1, 662_1, 663_1, 664_1, 665_1, 666_1, 667_1, 668_1, 669_1, 670_1, 671_1, 672_1, 673_1, 674_1, 675_1, 676_1, 677_1, 678_1, 679_1, 679_2, 679_3, 679_4, 679_5, 680_1, 680_2, 680_3, 680_4, 680_5, 681_1, 681_2, 681_3, 681_4, 681_5, 682_1, 682_2, 682_3, 682_4, 682_5, 683_1, 683_2, 683_3, 683_4, 683_5, 684_1, 684_2, 684_3, 684_4, 684_5, 685_1, 685_2, 685_3, 685_4, 685_5, 686_1, 686_2, 686_3, 686_4, 686_5, 687_1, 687_2, 687_3, 687_4, 687_5, 688_1, 688_2, 688_3, 688_4, 688_5, 689_1, 689_2, 689_3, 689_4, 689_5, 690_1, 690_2, 690_3, 690_4, 690_5, 691_1, 691_2, 692_1, 692_2, 692_3, 692_4, 692_5, 693_1, 693_2, 693_3, 693_4, 693_5, 694_1, 694_2, 694_3, 694_4, 694_5, 695_1, 695_2, 695_3, 695_4, 695_5, 696_1, 696_2, 696_3, 696_4, 696_5, 697_1, 697_2, 697_3, 697_4, 697_5, 698_1, 698_2, 698_3, 698_4, 698_5, 699_1, 699_2, 699_3, 699_4, 699_5, 700_1, 700_2, 700_3, 700_4, 700_5, 701_1, 701_2, 701_3, 701_4, 701_5, 702_1, 702_2, 702_3, 702_4, 702_5, 703_1, 703_2, 703_3, 703_4, 703_5, 704_1, 704_2, 704_3, 704_4, 704_5, 705_1, 705_2, 705_3, 705_4, 705_5, 706_1, 706_2, 706_3, 706_4, 706_5, 707_1, 707_2, 707_3, 707_4, 707_5, 708_1, 708_2, 708_3, 708_4, 708_5, 709_1, 709_2, 709_3, 709_4, 709_5, 710_1, 710_2, 710_3, 710_4, 710_5, 711_1, 711_2, 711_3, 711_4, 711_5, 712_1, 712_2, 712_3, 712_4, 712_5, 713_1, 713_2, 713_3, 713_4, 713_5, 714_1, 714_2, 714_3, 714_4, 714_5, 715_1, 715_2, 715_3, 715_4, 715_5, 716_1, 716_2, 716_3, 716_4, 716_5, 717_1, 717_2, 717_3, 717_4, 717_5, 718_1, 718_2, 719_1, 719_2, 719_3, 719_4, 719_5, 720_1, 720_2, 720_3, 720_4, 720_5, 721_1, 721_2, 721_3, 721_4, 721_5, 722_1, 722_2, 722_3, 722_4, 722_5, 723_1, 723_2, 723_3, 723_4, 723_5, 724_1, 724_2, 724_3, 724_4, 724_5, 725_1, 725_2, 725_3, 725_4, 725_5, 726_1, 726_2, 726_3, 726_4, 726_5, 727_1, 727_2, 727_3, 727_4, 727_5, 728_1, 728_2, 728_3, 728_4, 728_5, 729_1, 729_2, 729_3, 729_4, 729_5, 730_1, 730_2, 730_3, 730_4, 730_5, 731_1, 731_2, 731_3, 731_4, 731_5, 732_1, 732_2, 732_3, 732_4, 732_5, 733_1, 733_2, 733_3, 733_4, 733_5, 734_1, 734_2, 734_3, 734_4, 734_5, 735_1, 735_2, 735_3, 735_4, 735_5, 736_1, 736_2, 736_3, 736_4, 736_5, 737_1, 737_2, 737_3, 737_4, 737_5, 738_1, 738_2, 738_3, 738_4, 738_5, 738_6, 739_1, 739_2, 739_3, 739_4, 739_5, 740_1, 740_2, 740_3, 740_4, 740_5, 741_1, 741_2, 741_3, 741_4, 741_5, 742_1, 742_2, 742_3, 743_1, 743_2, 743_3, 743_4, 743_5, 744_1, 744_2, 744_3, 744_4, 744_5, 745_1, 745_2, 745_3, 745_4, 745_5, 746_1, 746_2, 746_3, 747_1, 747_2, 747_3, 747_4, 747_5, 748_1, 748_2, 748_3, 748_4, 748_5, 749_1, 749_2, 749_3, 749_4, 749_5, 750_1, 750_2, 750_3, 750_4, 751_1, 751_2, 751_3, 751_4, 751_5, 752_1, 752_2, 752_3, 752_4, 752_5, 753_1, 753_2, 753_3, 753_4, 753_5, 754_1, 754_2, 754_3, 754_4, 754_5, 755_1, 755_2, 755_3, 755_4, 755_5, 756_1, 756_2, 756_3, 756_4, 756_5, 757_1, 757_2, 757_3, 757_4, 757_5, 758_1, 758_2, 758_3, 758_4, 758_5, 759_1, 759_2, 759_3, 759_4, 759_5, 760_1, 760_2, 760_3, 760_4, 760_5, 761_1, 761_2, 761_3, 761_4, 761_5, 762_1, 762_2, 762_3, 762_4, 762_5, 763_1, 763_2, 763_3, 763_4, 763_5, 764_1, 764_2, 764_3, 764_4, 764_5, 765_1, 765_2, 765_3, 765_4, 765_5, 766_1, 766_2, 766_3, 766_4, 766_5, 767_1, 767_2, 767_3, 767_4, 767_5, 768_1, 768_2, 768_3, 768_4, 768_5, 769_1, 769_2, 769_3, 769_4, 769_5, 770_1, 770_2, 770_3, 770_4, 770_5, 771_1, 771_2, 771_3, 771_4, 771_5, 772_1, 772_2, 772_3, 772_4, 772_5, 773_1, 773_2, 773_3, 773_4, 773_5, 774_1, 774_2, 774_3, 774_4, 774_5, 775_1, 775_2, 775_3, 775_4, 775_5, 776_1, 776_2, 776_3, 776_4, 776_5, 777_1, 777_2, 777_3, 777_4, 777_5, 778_1, 778_2, 778_3, 778_4, 778_5, 779_1, 779_2, 779_3, 779_4, 779_5, 780_1, 780_2, 780_3, 780_4, 780_5, 781_1, 782_1, 782_2, 782_3, 782_4, 782_5, 783_1, 783_2, 783_3, 783_4, 783_5, 784_1, 784_2, 784_3, 784_4, 784_5, 785_1, 786_1, 786_2, 786_3, 786_4, 786_5, 787_1, 787_2, 787_3, 787_4, 787_5, 788_1, 788_2, 788_3, 788_4, 788_5, 789_1, 789_2, 789_3, 789_4, 789_5, 790_1, 790_2, 790_3, 790_4, 790_5, 791_1, 791_2, 791_3, 791_4, 791_5, 792_1, 792_2, 792_3, 792_4, 792_5, 793_1, 793_2, 793_3, 793_4, 793_5, 794_1, 794_2, 794_3, 794_4, 794_5, 795_1, 795_2, 795_3, 795_4, 795_5, 796_1, 796_2, 796_3, 796_4, 796_5, 797_1, 797_2, 797_3, 797_4, 797_5, 798_1, 798_2, 798_3, 798_4, 798_5, 799_1, 799_2, 799_3, 799_4, 799_5, 800_1, 800_2, 800_3, 800_4, 800_5, 801_1, 801_2, 801_3, 801_4, 801_5, 802_1, 802_2, 802_3, 802_4, 802_5, 803_1, 803_2, 803_3, 803_4, 803_5, 804_1, 804_2, 804_3, 804_4, 804_5, 805_1, 805_2, 805_3, 805_4, 805_5, 806_1, 806_2, 806_3, 806_4, 806_5, 807_1, 807_2, 807_3, 807_4, 807_5, 808_1, 808_2, 808_3, 808_4, 808_5, 809_1, 809_2, 809_3, 809_4, 809_5, 810_1, 810_2, 810_3, 810_4, 810_5, 811_1, 811_2, 811_3, 811_4, 811_5, 812_1, 812_2, 812_3, 812_4, 812_5, 813_1, 813_2, 813_3, 813_4, 813_5, 814_1, 814_2, 814_3, 814_4, 814_5, 815_1, 815_2, 815_3, 815_4, 815_5, 816_1, 816_2, 816_3, 816_4, 816_5, 816_6, 817_1 and 818_1.
• 86. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 155_1 or 165_1.
• 87. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO 169_52, 169_50 or 169_56.
• 88. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 172_1, 272_1, 572_7, 572_6 or 572_5.
• 89. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 175_1.
• 90. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 178_1.
• 91. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 573_8, 186_1 or 187_1.
• 92. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 186_1.
• 93. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 200_1, 204_1, 206_1, 35_2 or 209_1.
• 94. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 585_1, 585_8, 586_9, 586_5, 586_8, 586_4 or 586_6.
• 95. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 233_1.
• 96. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 237_8 or 590_13.
• 97. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 220_1.
• 98. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 591_1, 592_2, 592_4 or 241_9.
• 99. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 597_4, 598_4, 39_1 or 602_1.
• 100. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 39_1.
• 101. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 611_7.
• 102. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 271_1 or 278_1.
• 103. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 616_4, 621_2, 621_1, 622_3, 622_5, 622_4, 624_3, 624_5, 287_1, 625_6, 626_7, 626_8, 626_9, 48_1, 631_6, 631_1, 303_1, 304_6 or 304_10.
• 104. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 636_8.
• 105. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 638_8, 639_5, 331_1 or 640_4.
• 106. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 359_1, 361_1, 361_5, 362_1 or 641_5.
• 107. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 378_1, 379_1 or 399_1.
• 108. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from the group consisting of CMP-ID-NO: 403_1, 405_1, 642_12, 642_13, 644_3 or 646_16.
• 109. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 85_1 or 425_5.
• 110. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 116_1.
• 111. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 123_1 or 124_1.
• 112. The oligonucleotide of embodiment 85, wherein the oligonucleotide is selected from CMP-ID-NO: 126_2.
• 113. A conjugate comprising the oligonucleotide according to any one of claims 1-112, and at least one conjugate moiety covalently attached to said oligonucleotide.
• 114. The oligonucleotide conjugate of embodiment 113, wherein the conjugate moiety is selected from carbohydrates, cell surface receptor ligands, drug substances, hormones, lipophilic substances, polymers, proteins, peptides, toxins, vitamins, viral proteins or combinations thereof.
• 115. The oligonucleotide conjugate of embodiment 113 or 114, wherein the conjugate moiety is an antibody or antibody fragment.
• 116. The oligonucleotide conjugate of embodiment 115, wherein the antibody or antibody fragment has affinity to the transferrin receptor.
• 117. The oligonucleotide conjugate of embodiment 113-115, comprising a linker which is positioned between the oligonucleotide and the conjugate moiety.
• 118. The oligonucleotide conjugate of embodiment 117, wherein the linker is a physiologically labile linker.
• 119. The oligonucleotide conjugate of embodiment 118, wherein the physiologically labile linker is nuclease susceptible linker.
• 120. The oligonucleotide conjugate of embodiment 118 or 119, wherein the oligonucleotide has the formula D-F-G-F′ or F-G-F′-D′, wherein F, F′ and G are as defined in embodiments 73-80 and D or D′ comprises 1, 2 or 3 DNA nucleosides with phosphorothioate internucleoside linkages.
• 121. The oligonucleotide conjugate of embodiment 113-120, which display improved uptake into the brain of the conjugate oligonucleotide as compared to an unconjugated oligonucleotide.
• 122. A pharmaceutical composition comprising the oligonucleotide of embodiment 1-112 or a conjugate of embodiment 113-121 and a pharmaceutically acceptable diluent, carrier, salt and/or adjuvant.
• 123. A method for manufacturing the oligonucleotide of embodiment 1-112, comprising reacting nucleotide units thereby forming covalently linked contiguous nucleotide units comprised in the oligonucleotide.
• 124. The method of embodiment 123, further comprising reacting the contiguous nucleotide sequence with a non-nucleotide conjugation moiety.
• 125. A method for manufacturing the composition of embodiment 122, comprising mixing the oligonucleotide with a pharmaceutically acceptable diluent, carrier, salt and/or adjuvant.
• 126. An in vivo or in vitro method for inducing UBE3A expression in a target cell where expression of paternal UBE3A is suppressed, said method comprising administering an oligonucleotide of any one of embodiments 1-112 or a conjugate of embodiment 113-121 or the pharmaceutical composition of embodiment 122 in an effective amount to said cell.
• 127. The method of embodiment 126, wherein the expression of UBE3A is increased by at least 40% compared to a control.
• 128. The method of embodiment 126 or 127, wherein the level of the SNHG14 transcript downstream of SNORD109B is reduced by at least 30% compared to a control.
• 129. The method of embodiment 126-128, wherein the target cell is a neuronal cell.
• 130. The method of embodiment 126-129, wherein the expression of SNORD115 is not significantly affected compared to a control.
• 131. A method for treating or preventing a disease comprising administering a therapeutically or prophylactically effective amount of an oligonucleotide of embodiment 1-112 or a conjugate of embodiment 113-121 or the pharmaceutical composition of embodiment 122 to a subject suffering from or susceptible to the disease.
• 132. The oligonucleotide of embodiment 1-112 or a conjugate of embodiment 113-121 or the pharmaceutical composition of embodiment 122, for use as a medicament for treatment or prevention of a disease in a subject.
• 133. Use of the oligonucleotide of oligonucleotide of embodiment 1-112 or a conjugate of embodiment 113-121 for the preparation of a medicament for treatment or prevention of a disease in a subject.
• 134. The method, the oligonucleotide or the use of embodiments 131-133, wherein the disease is associated with in vivo activity of UBE3A.
• 135. The method, the oligonucleotide or the use of embodiments 131-134, wherein the disease is associated with reduced expression of UBE3A and/or reduced activity of UBE3A in neuronal cells.
• 136. The method, the oligonucleotide or the use of embodiment 135, wherein the reduced expression of UBE3A and/or reduced activity of UBE3A is due to mutations in the maternal allele of the UBE3A gene.
• 137. The method, the oligonucleotide or the use of embodiments 134-136, wherein the UBE3A expression is increased by at least 30%, or at least 50%, or at least 70%, or at least 90%, or at least 100%, or at least 150% or at least 200%, compared to the expression without the oligonucleotide of embodiment 1-112 or a conjugate of embodiment 113-121 or the pharmaceutical composition of embodiment 122.
• 138. The method, the oligonucleotide or the use of embodiments 131-137, wherein the disease is Angelman syndrome.
• 139. The method, the oligonucleotide or the use of embodiments 131-138, wherein the subject is a mammal.
• 140. The method, the oligonucleotide or the use of embodiment 139, wherein the mammal is human.
• 141. The method, the oligonucleotide or the use of embodiment 139 or 140, wherein the subject is an infant or a juvenile.
EXAMPLES
• Materials and methods

• TABLE 3
  List of oligonucleotides or contiguous nucleobase sequences complementary to SEQ
  ID NO: 1 (motif sequences indicated by SEQ ID NO), oligonucleotide designs made from these,
  as well as specific oligonucleotide compounds (indicated by CMP ID NO) designed based on
  the motif sequence.

  						Start
  Seq				CMP		SEQ ID
  ID NO	Motif	Design	Compound	ID NO	ΔG°	NO 1

  4	AACTTCATCAATATTTCCC	3-13-3	AACttcatcaatatttCCC	4_1	-23.36	1677
  4	AACTTCATCAATATTTCCC	2-15-2	AActtcatcaatatttcCC	4_2	-19.60	1677
  5	ACTTCATCAATATTTCCC	3-12-3	ACTtcatcaatatttCCC	5_1	-23.80	1677
  5	ACTTCATCAATATTTCCC	2-14-2	ACttcatcaatatttcCC	5_2	-20.24	1677
  6	CAACTTCATCAATATTTCCC	2-14-4	CAacttcatcaatattTCCC	6_1	-25.64	1677
  6	CAACTTCATCAATATTTCCC	2-16-2	CAacttcatcaatatttcCC	6_2	-22.28	1677
  7	CAACTTCATCAATATTTCC	4-13-2	CAACttcatcaatatttCC	7_1	-21.47	1678
  7	CAACTTCATCAATATTTCC	2-15-2	CAacttcatcaatatttCC	7_2	-19.46	1678
  8	CCAACTTCATCAATATTTCC	3-14-3	CCAacttcatcaatattTCC	8_1	-25.64	1678
  9	CCCAACTTCATCAATATTTC	4-14-2	CCCAacttcatcaatattTC	9_1	-25.64	1679
  10	ACCCAACTTCATCAATATTT	2-16-2	ACccaacttcatcaatatTT	10_1	-20.05	1680
  11	CCCAACTTCATCAATATTT	4-13-2	CCCAacttcatcaatatTT	11_1	-23.96	1680
  11	CCCAACTTCATCAATATTT	2-15-2	CCcaacttcatcaatatTT	11_2	-20.28	1680
  12	ACCCAACTTCATCAATATT	4-13-2	ACCCaacttcatcaataTT	12_1	-23.64	1681
  12	ACCCAACTTCATCAATATT	2-15-2	ACccaacttcatcaataTT	12_2	-19.18	1681
  13	CCCAACTTCATCAATATT	4-12-2	CCCAacttcatcaataTT	13_1	-23.09	1681
  13	CCCAACTTCATCAATATT	2-14-2	CCcaacttcatcaataTT	13_2	-19.41	1681
  14	TACCCAACTTCATCAATAT	2-15-2	TAcccaacttcatcaatAT	14_1	-19.31	1682
  15	TACCCAACTTCATCAATA	2-14-2	TAcccaacttcatcaaTA	15_1	-19.14	1683
  16	TTACCCAACTTCATCAATA	2-15-2	TTacccaacttcatcaaTA	16_1	-19.74	1683
  17	TTTACCCAACTTCATCAAT	4-13-2	TTTAcccaacttcatcaAT	17_1	-21.68	1684
  17	TTTACCCAACTTCATCAAT	2-15-2	TTtacccaacttcatcaAT	17_2	-19.22	1684
  18	ATACTTTACCCAACTTCAT	3-13-3	ATActttacccaacttCAT	18_1	-23.44	1688
  18	ATACTTTACCCAACTTCAT	2-15-2	ATactttacccaacttcAT	18_2	-20.13	1688
  19	TACTTTACCCAACTTCAT	3-12-3	TACtttacccaacttCAT	19_1	-22.78	1688
  19	TACTTTACCCAACTTCAT	2-14-2	TActttacccaacttcAT	19_2	-19.30	1688
  20	TTATACTTTACCCAACTTCA	2-16-2	TTatactttacccaacttCA	20_1	-21.40	1689
  21	TCACTGTTCTGACTTT	3-10-3	TCActgttctgacTTT	21_1	-19.11	1712
  22	TTCAATCTCTATCTCATCAT	2-16-2	TTcaatctctatctcatcAT	22_1	-19.42	4169
  23	CTTCAATCTCTATCTCATCA	4-14-2	CTTCaatctctatctcatCA	23_1	-24.21	4170
  23	CTTCAATCTCTATCTCATCA	2-16-2	CTtcaatctctatctcatCA	23_2	-22.04	4170
  24	TTCAATCTCTATCTCATCA	2-15-2	TTcaatctctatctcatCA	24_1	-19.44	4170
  25	CTTCAATCTCTATCTCATC	2-15-2	CTtcaatctctatctcaTC	25_1	-19.87	4171
  26	ACTTCAATCTCTATCTCAT	3-13-3	ACTtcaatctctatctCAT	26_1	-22.36	4172
  26	ACTTCAATCTCTATCTCAT	2-15-2	ACttcaatctctatctcAT	26_2	-19.08	4172
  27	CACTTCAATCTCTATCTCAT	2-16-2	CActtcaatctctatctcAT	27_1	-20.98	4172
  28	ACTTCAATCTCTATCTCA	2-12-4	ACttcaatctctatCTCA	28_1	-21.96	4173
  28	ACTTCAATCTCTATCTCA	2-14-2	ACttcaatctctatctCA	28_2	-19.10	4173
  29	CACTTCAATCTCTATCTCA	2-13-4	CActtcaatctctatCTCA	29_1	-23.86	4173
  29	CACTTCAATCTCTATCTCA	2-15-2	CActtcaatctctatctCA	29_2	-21.00	4173
  30	ACACTTCAATCTCTATCTC	2-15-2	ACacttcaatctctatcTC	30_1	-19.38	4174
  31	TACACTTCAATCTCTATCTC	2-14-4	TAcacttcaatctctaTCTC	31_1	-23.31	4174
  31	TACACTTCAATCTCTATCTC	2-16-2	TAcacttcaatctctatcTC	31_2	-20.53	4174
  32	TACACTTCAATCTCTATCT	4-13-2	TACActtcaatctctatCT	32_1	-22.34	4175
  33	CTTTGTCTCTCTTTACT	2-13-2	CTttgtctctctttaCT	33_1	-19.36	4374
  34	TATACCTTTCTTTAACCC	3-12-3	TATacctttctttaaCCC	34_1	-24.89	8118
  34	TATACCTTTCTTTAACCC	2-14-2	TAtacctttctttaacCC	34_2	-20.83	8118
  34	TATACCTTTCTTTAACCC	1-3-1-7-1-1-1-1-2	TataCctttcttTaAcCC	34_3	-21.63	8116
  34	TATACCTTTCTTTAACCC	1-4-1-6-1-3-2	TatacCtttcttTaacCC	34_4	-21.31	8116
  34	TATACCTTTCTTTAACCC	1-2-1-1-1-7-2-1-2	TatAcCtttctttAAcCC	34_5	-21.51	8116
  34	TATACCTTTCTTTAACCC	2-3-1-7-1-2-2	TAtacCtttctttAacCC	34_6	-21.84	8116
  34	TATACCTTTCTTTAACCC	2-13-3	TAtacctttctttaaCCC	34_7	-23.21	8116
  35	TGTTTATACCCTTTCC	2-12-2	TGtttataccctttCC	35_1	-20.33	9212
  35	TGTTTATACCCTTTCC	4-10-2	TGTTtataccctttCC	35_2	-22.69	9212
  36	TCTCCTTTATGACTCC	2-10-4	TCtcctttatgaCTCC	36_1	-23.29	10839
  37	CTTCTCCTTTATGACTC	2-13-2	CTtctcctttatgacTC	37_1	-19.26	10840
  38	CCATTTATTTCCATTTATT	4-13-2	CCATttatttccatttaTT	38_1	-22.32	15567
  38	CCATTTATTTCCATTTATT	2-15-2	CCatttatttccatttaTT	38_2	-19.61	15567
  38	CCATTTATTTCCATTTATT	1-2-1-9-2-1-3	CcaTttatttccaTTtATT	38_3	-20.02	15567
  38	CCATTTATTTCCATTTATT	1-1-1-1-1-8-1-1-1-1-2	CcAtTtatttccaTtTaTT	38_4	-18.95	15567
  38	CCATTTATTTCCATTTATT	2-2-1-8-1-3-2	CCatTtatttccaTttaTT	38_5	-20.35	15567
  38	CCATTTATTTCCATTTATT	1-2-3-6-1-3-3	CcaTTTatttccAtttATT	38_6	-20.87	15567
  39	CTTTCCATTTATTTCCATTT	2-14-4	CTttccatttatttccATTT	39_1	-23.14	15570
  39	CTTTCCATTTATTTCCATTT	1-13-1-1-1-1-2	CtttccatttatttCcAtTT	39_2	-20.96	15570
  39	CTTTCCATTTATTTCCATTT	1-13-1-3-2	CtttccatttatttCcatTT	39_3	-20.91	15570
  39	CTTTCCATTTATTTCCATTT	1-3-1-1-1-11-2	CtttCcAtttatttccatTT	39_4	-20.96	15570
  39	CTTTCCATTTATTTCCATTT	1-1-1-3-1-9-1-1-2	CtTtccAtttatttccAtTT	39_5	-20.54	15570
  40	TCTTTCCATTTATTTCCATT	2-14-4	TCtttccatttatttcCATT	40_1	-24.62	15571
  40	TCTTTCCATTTATTTCCATT	2-13-1-1-3	TCtttccatttatttCcATT	40_2	-23.39	15571
  40	TCTTTCCATTTATTTCCATT	2-13-1-2-2	TCtttccatttatttCcaTT	40_3	-22.53	15571
  40	TCTTTCCATTTATTTCCATT	2-14-1-1-2	TCtttccatttatttcCaTT	40_4	-22.34	15571
  40	TCTTTCCATTTATTTCCATT	2-3-1-11-3	TCtttCcatttatttccATT	40_5	-23.39	15571
  40	TCTTTCCATTTATTTCCATT	2-4-1-10-3	TCtttcCatttatttccATT	40_6	-23.20	15571
  40	TCTTTCCATTTATTTCCATT	2-3-1-12-2	TCtttCcatttatttccaTT	40_7	-22.53	15571
  40	TCTTTCCATTTATTTCCATT	2-4-1-11-2	TCtttcCatttatttccaTT	40_8	-22.34	15571
  41	ATTACCCATCCGTTCT	2-12-2	ATtacccatccgttCT	41_1	-21.15	21965
  42	GCATTAGGCACATTACAT	3-12-3	GCAttaggcacattaCAT	42_1	-23.96	22211
  43	ATTATTATTTAACCTTCCTA	2-16-2	ATtattatttaaccttccTA	43_1	-19.28	30451
  44	ACATTATTATTTAACCTTCC	4-14-2	ACATtattatttaaccttCC	44_1	-22.84	30453
  44	ACATTATTATTTAACCTTCC	2-16-2	ACattattatttaaccttCC	44_2	-20.13	30453
  45	CATTATTATTTAACCTTCC	4-13-2	CATTattatttaaccttCC	45_1	-22.04	30453
  45	CATTATTATTTAACCTTCC	2-15-2	CAttattatttaaccttCC	45_2	-19.55	30453
  46	CCTCTGCTTATAACTTT	2-13-2	CCtctgcttataactTT	46_1	-19.15	30699
  47	CTACTATACTTTCCTCT	2-11-4	CTactatactttcCTCT	47_1	-22.32	30711
  48	GTTCTACTATACTTTCC	4-11-2	GTTCtactatactttCC	48_1	-21.69	30714
  48	GTTCTACTATACTTTCC	2-13-2	GTtctactatactttCC	48_2	-19.21	30714
  48	GTTCTACTATACTTTCC	1-2-1-7-2-2-2	GttCtactataCTttCC	48_3	-20.83	30712
  48	GTTCTACTATACTTTCC	2-9-1-3-2	GTtctactataCtttCC	48_4	-20.20	30712
  48	GTTCTACTATACTTTCC	1-2-1-9-1-1-2	GttCtactatactTtCC	48_5	-18.95	30712
  48	GTTCTACTATACTTTCC	2-1-1-10-3	GTtCtactatacttTCC	48_6	-21.18	30712
  48	GTTCTACTATACTTTCC	1-3-1-10-2	GttcTactatactttCC	48_7	-18.61	30712
  49	CACCTGATAACAGACCCT	3-12-3	CACctgataacagacCCT	49_1	-26.38	36068
  50	CACCTGATAACAGACC	3-10-3	CACctgataacagACC	50_1	-21.10	36070
  51	CCCACCAAAGGATATATT	3-12-3	CCCaccaaaggatatATT	51_1	-23.47	37208
  52	ACCAGCTACAGGAACCTC	3-12-3	ACCagctacaggaacCTC	52_1	-26.57	46132
  53	CTATATCTCACTCCTATTT	4-13-2	CTATatctcactcctatTT	53_1	-23.07	48143
  53	CTATATCTCACTCCTATTT	2-13-4	CTatatctcactcctATTT	53_2	-22.12	48143
  54	CTATATCTCACTCCTATT	2-14-2	CTatatctcactcctaTT	54_1	-19.40	48144
  54	CTATATCTCACTCCTATT	2-12-4	CTatatctcactccTATT	54_2	-22.28	48144
  54	CTATATCTCACTCCTATT	3-12-3	CTAtatctcactcctATT	54_3	-21.44	48144
  55	CTACTATATCTCACTCCTAT	2-16-2	CTactatatctcactcctAT	55_1	-22.00	48145
  55	CTACTATATCTCACTCCTAT	2-14-4	CTactatatctcactcCTAT	55_2	-25.54	48145
  56	TACTATATCTCACTCCTAT	2-13-4	TActatatctcactcCTAT	56_1	-23.29	48145
  57	CTACTATATCTCACTCCTA	2-15-2	CTactatatctcactccTA	57_1	-21.91	48146
  58	TACTATATCTCACTCCTA	2-14-2	TActatatctcactccTA	58_1	-19.66	48146
  58	TACTATATCTCACTCCTA	2-12-4	TActatatctcactCCTA	58_2	-23.59	48146
  58	TACTATATCTCACTCCTA	3-12-3	TACtatatctcactcCTA	58_3	-22.62	48146
  59	CTACTATATCTCACTCCT	2-14-2	CTactatatctcactcCT	59_1	-21.25	48147
  59	CTACTATATCTCACTCCT	4-12-2	CTACtatatctcactcCT	59_2	-23.87	48147
  60	CTACTATATCTCACTCC	2-13-2	CTactatatctcactCC	60_1	-20.13	48148
  60	CTACTATATCTCACTCC	2-11-4	CTactatatctcaCTCC	60_2	-23.00	48148
  60	CTACTATATCTCACTCC	3-11-3	CTActatatctcacTCC	60_3	-22.56	48148
  61	CCTACTATATCTCACTC	2-11-4	CCtactatatctcACTC	61_1	-21.93	48149
  62	CTCCTACTATATCTCACTC	4-13-2	CTCCtactatatctcacTC	62_1	-25.69	48149
  63	TCCTACTATATCTCACTC	3-12-3	TCCtactatatctcaCTC	63_1	-23.88	48149
  64	CTCCTACTATATCTCACT	4-12-2	CTCCtactatatctcaCT	64_1	-24.87	48150
  64	CTCCTACTATATCTCACT	3-12-3	CTCctactatatctcACT	64_2	-22.93	48150
  65	TTTCCTCTCCTACTATATC	2-15-2	TTtcctctcctactataTC	65_1	-21.23	48155
  66	ATCCATATCCTTTCCT	3-10-3	ATCcatatcctttCCT	66_1	-24.02	48168
  67	CATCCATATCCTTTCCT	4-11-2	CATCcatatcctttcCT	67_1	-24.94	48168
  68	ATCATCCATATCCTTTCC	4-12-2	ATCAtccatatcctttCC	68_1	-25.69	48169
  69	CATCATCCATATCCTTTC	4-12-2	CATCatccatatccttTC	69_1	-23.32	48170
  69	CATCATCCATATCCTTTC	2-14-2	CAtcatccatatccttTC	69_2	-20.72	48170
  69	CATCATCCATATCCTTTC	2-12-4	CAtcatccatatccTTTC	69_3	-22.56	48170
  70	TACATCATCCATATCCTTTC	2-16-2	TAcatcatccatatccttTC	70_1	-22.45	48170
  70	TACATCATCCATATCCTTTC	4-14-2	TACAtcatccatatccttTC	70_2	-25.00	48170
  70	TACATCATCCATATCCTTTC	2-14-4	TAcatcatccatatccTTTC	70_3	-24.29	48170
  71	ACATCATCCATATCCTTT	3-12-3	ACAtcatccatatccTTT	71_1	-22.11	48171
  72	CATCATCCATATCCTTT	2-13-2	CAtcatccatatcctTT	72_1	-19.04	48171
  72	CATCATCCATATCCTTT	4-11-2	CATCatccatatcctTT	72_2	-21.64	48171
  73	TACATCATCCATATCCTTT	2-15-2	TAcatcatccatatcctTT	73_1	-20.76	48171
  73	TACATCATCCATATCCTTT	2-13-4	TAcatcatccatatcCTTT	73_2	-23.36	48171
  73	TACATCATCCATATCCTTT	3-13-3	TACatcatccatatccTTT	73_3	-22.88	48171
  74	ATACATCATCCATATCCTT	2-15-2	ATacatcatccatatccTT	74_1	-20.80	48172
  74	ATACATCATCCATATCCTT	4-13-2	ATACatcatccatatccTT	74_2	-23.12	48172
  75	TACATCATCCATATCCTT	2-14-2	TAcatcatccatatccTT	75_1	-19.97	48172
  75	TACATCATCCATATCCTT	4-12-2	TACAtcatccatatccTT	75_2	-22.52	48172
  76	TATACATCATCCATATCCTT	2-16-2	TAtacatcatccatatccTT	76_1	-21.36	48172
  77	ATACATCATCCATATCCT	3-12-3	ATAcatcatccatatCCT	77_1	-24.15	48173
  77	ATACATCATCCATATCCT	2-14-2	ATacatcatccatatcCT	77_2	-20.55	48173
  77	ATACATCATCCATATCCT	2-13-3	ATacatcatccatatCCT	77_3	-22.92	48173
  78	ATATACATCATCCATATCCT	2-16-2	ATatacatcatccatatcCT	78_1	-22.04	48173
  79	TACATCATCCATATCCT	2-11-4	TAcatcatccataTCCT	79_1	-23.21	48173
  79	TACATCATCCATATCCT	2-13-2	TAcatcatccatatcCT	79_2	-19.71	48173
  79	TACATCATCCATATCCT	4-11-2	TACAtcatccatatcCT	79_3	-22.27	48173
  80	TATACATCATCCATATCCT	2-15-2	TAtacatcatccatatcCT	80_1	-21.11	48173
  80	TATACATCATCCATATCCT	3-13-3	TATacatcatccatatCCT	80_2	-25.15	48173
  80	TATACATCATCCATATCCT	4-13-2	TATAcatcatccatatcCT	80_3	-24.01	48173
  81	ATACATCATCCATATCC	3-11-3	ATAcatcatccataTCC	81_1	-21.79	48174
  82	ATATACATCATCCATATCC	4-13-2	ATATacatcatccatatCC	82_1	-23.73	48174
  82	ATATACATCATCCATATCC	2-15-2	ATatacatcatccatatCC	82_2	-20.93	48174
  83	TATACATCATCCATATCC	2-14-2	TAtacatcatccatatCC	83_1	-20.00	48174
  83	TATACATCATCCATATCC	4-12-2	TATAcatcatccatatCC	83_2	-22.90	48174
  84	TATATACATCATCCATATCC	2-16-2	TAtatacatcatccatatCC	84_1	-21.49	48174
  84	TATATACATCATCCATATCC	4-14-2	TATAtacatcatccatatCC	84_2	-24.29	48174
  85	GCTTCATATTTCTCCA	2-12-2	GCttcatatttctcCA	85_1	-20.44	49345
  85	GCTTCATATTTCTCCA	2-11-3	GCttcatatttctCCA	85_2	-22.81	49345
  86	CATCTTGTTCTTTACCT	2-13-2	CAtcttgttctttacCT	86_1	-19.67	49581
  87	TATATTCACCATTGCC	2-10-4	TAtattcaccatTGCC	87_1	-22.70	49724
  88	CCTTATATTCACCATTG	2-13-2	CCttatattcaccatTG	88_1	-19.44	49726
  88	CCTTATATTCACCATTG	2-11-4	CCttatattcaccATTG	88_2	-21.25	49726
  89	CCTCCTTATATTCACC	4-10-2	CCTCcttatattcaCC	89_1	-24.64	49730
  go	CCCTTCCTTTATTCAA	3-10-3	CCCttcctttattCAA	90_1	-23.86	50189
  gi	CCTTACTGTTAAATCCT	2-13-2	CCttactgttaaatcCT	91_1	-19.81	50475
  92	CAGGCAGATAACCTCCAA	3-12-3	CAGgcagataacctcCAA	92_1	-25.31	52419
  93	CAGCAGGCAGATAACCTC	3-12-3	CAGcaggcagataacCTC	93_1	-25.88	52422
  94	CGAATCTTGACATACAGG	3-12-3	CGAatcttgacatacAGG	94_1	-21.47	53955
  95	CTCATACTTGCTTTAAT	4-11-2	CTCAtacttgctttaAT	95_1	-19.10	60821
  95	CTCATACTTGCTTTAAT	2-13-2	CTcatacttgctttaAT	95_2	-16.35	60821
  96	ACATCTCATACTTGCTT	2-11-4	ACatctcatacttGCTT	96_1	-21.31	60825
  96	ACATCTCATACTTGCTT	2-13-2	ACatctcatacttgcTT	96_2	-17.66	60825
  96	ACATCTCATACTTGCTT	2-12-3	ACatctcatacttgCTT	96_3	-19.52	60825
  97	ACATCTCATACTTGCT	2-10-4	ACatctcatactTGCT	97_1	-21.18	60826
  97	ACATCTCATACTTGCT	2-12-2	ACatctcatacttgCT	97_2	-17.70	60826
  97	ACATCTCATACTTGCT	2-11-3	ACatctcatacttGCT	97_3	-19.49	60826
  97	ACATCTCATACTTGCT	4-10-2	ACATctcatacttgCT	97_4	-20.48	60826
  98	TACATCTCATACTTGCT	2-11-4	TAcatctcatactTGCT	98_1	-22.33	60826
  98	TACATCTCATACTTGCT	2-13-2	TAcatctcatacttgCT	98_2	-18.85	60826
  98	TACATCTCATACTTGCT	4-11-2	TACAtctcatacttgCT	98_3	-21.40	60826
  gg	CCTACATCTCATACTTGC	3-12-3	CCTacatctcatactTGC	gg_1	-26.29	60827
  gg	CCTACATCTCATACTTGC	2-14-2	CCtacatctcatacttGC	99_2	-22.98	60827
  gg	CCTACATCTCATACTTGC	2-13-3	CCtacatctcatactTGC	99_3	-24.67	60827
  gg	CCTACATCTCATACTTGC	2-12-4	CCtacatctcatacTTGC	99_4	-25.70	60827
  100	CTACATCTCATACTTGC	3-11-3	CTAcatctcatactTGC	100_1	-22.33	60827
  100	CTACATCTCATACTTGC	2-13-2	CTacatctcatacttGC	100_2	-19.41	60827
  100	CTACATCTCATACTTGC	2-12-3	CTacatctcatactTGC	100_3	-21.10	60827
  101	TACATCTCATACTTGC	3-10-3	TACatctcatactTGC	101_1	-19.94	60827
  101	TACATCTCATACTTGC	2-12-2	TAcatctcatacttGC	101_2	-17.15	60827
  101	TACATCTCATACTTGC	2-11-3	TAcatctcatactTGC	101_3	-18.85	60827
  101	TACATCTCATACTTGC	4-10-2	TACAtctcatacttGC	101_4	-19.71	60827
  102	CCTACATCTCATACTTG	4-11-2	CCTAcatctcatactTG	102_1	-22.52	60828
  102	CCTACATCTCATACTTG	2-13-2	CCtacatctcatactTG	102_2	-19.67	60828
  102	CCTACATCTCATACTTG	3-12-2	CCTacatctcatactTG	102_3	-21.29	60828
  102	CCTACATCTCATACTTG	3-11-3	CCTacatctcatacTTG	102_4	-22.31	60828
  103	ACCTACATCTCATACTT	3-11-3	ACCtacatctcataCTT	103_1	-21.93	60829
  103	ACCTACATCTCATACTT	2-13-2	ACctacatctcatacTT	103_2	-17.76	60829
  103	ACCTACATCTCATACTT	2-11-4	ACctacatctcatACTT	103_3	-20.03	60829
  103	ACCTACATCTCATACTT	3-12-2	ACCtacatctcatacTT	103_4	-20.26	60829
  104	CCTACATCTCATACTT	3-10-3	CCTacatctcataCTT	104_1	-21.50	60829
  104	CCTACATCTCATACTT	2-12-2	CCtacatctcatacTT	104_2	-18.21	60829
  104	CCTACATCTCATACTT	2-10-4	CCtacatctcatACTT	104_3	-20.48	60829
  105	TACCTACATCTCATACTT	4-12-2	TACCtacatctcatacTT	105_1	-22.49	60829
  105	TACCTACATCTCATACTT	2-14-2	TAcctacatctcatacTT	105_2	-18.81	60829
  105	TACCTACATCTCATACTT	2-13-3	TAcctacatctcataCTT	105_3	-20.48	60829
  105	TACCTACATCTCATACTT	2-12-4	TAcctacatctcatACTT	105_4	-21.08	60829
  106	TTACCTACATCTCATACTT	3-13-3	TTAcctacatctcataCTT	106_1	-22.30	60829
  106	TTACCTACATCTCATACTT	2-15-2	TTacctacatctcatacTT	106_2	-19.40	60829
  106	TTACCTACATCTCATACTT	2-14-3	TTacctacatctcataCTT	106_3	-21.08	60829
  106	TTACCTACATCTCATACTT	2-13-4	TTacctacatctcatACTT	106_4	-21.67	60829
  107	ACCTACATCTCATACT	4-10-2	ACCTacatctcataCT	107_1	-21.72	60830
  107	ACCTACATCTCATACT	2-12-2	ACctacatctcataCT	107_2	-17.61	60830
  107	ACCTACATCTCATACT	3-11-2	ACCtacatctcataCT	107_3	-20.10	60830
  107	ACCTACATCTCATACT	2-10-4	ACctacatctcaTACT	107_4	-20.11	60830
  108	TACCTACATCTCATACT	4-11-2	TACCtacatctcataCT	108_1	-22.34	60830
  108	TACCTACATCTCATACT	2-13-2	TAcctacatctcataCT	108_2	-18.66	60830
  108	TACCTACATCTCATACT	3-12-2	TACctacatctcataCT	108_3	-19.85	60830
  108	TACCTACATCTCATACT	3-11-3	TACctacatctcatACT	108_4	-20.44	60830
  109	TTACCTACATCTCATACT	2-12-4	TTacctacatctcaTACT	109_1	-21.75	60830
  109	TTACCTACATCTCATACT	2-14-2	TTacctacatctcataCT	109_2	-19.25	60830
  109	TTACCTACATCTCATACT	3-13-2	TTAcctacatctcataCT	109_3	-20.48	60830
  109	TTACCTACATCTCATACT	3-12-3	TTAcctacatctcatACT	109_4	-21.08	60830
  110	TTACCTACATCTCATAC	3-11-3	TTAcctacatctcaTAC	110_1	-19.50	60831
  110	TTACCTACATCTCATAC	2-13-2	TTacctacatctcatAC	110_2	-16.37	60831
  111	GTTACCTACATCTCATA	2-11-4	GTtacctacatctCATA	111_1	-21.69	60832
  111	GTTACCTACATCTCATA	2-13-2	GTtacctacatctcaTA	111_2	-18.74	60832
  111	GTTACCTACATCTCATA	3-12-2	GTTacctacatctcaTA	111_3	-19.98	60832
  112	GTTACCTACATCTCAT	3-10-3	GTTacctacatctCAT	112_1	-20.69	60833
  112	GTTACCTACATCTCAT	2-12-2	GTtacctacatctcAT	112_2	-17.37	60833
  113	ATATACCCAAAGGCACCT	3-12-3	ATAtacccaaaggcaCCT	113_1	-25.99	62200
  114	TCTACTCATCCTTTAACTCA	2-14-4	TCtactcatcctttaaCTCA	114_1	-25.63	62251
  115	CCTTAATCTGTATCACT	2-13-2	CCttaatctgtatcaCT	115_1	-19.58	62286
  116	CCATACACAGCACATA	2-12-2	CCatacacagcacaTA	116_1	-19.04	62424
  117	CTCCATACACAGCACAT	2-13-2	CTccatacacagcacAT	117_1	-20.08	62425
  118	CAGAATAATTCTCCTCC	2-13-2	CAgaataattctcctCC	118_1	-19.86	62441
  119	GTCCTACATATATACC	4-10-2	GTCCtacatatataCC	119_1	-22.09	66380
  120	TGCTTCCTTACTAACC	4-10-2	TGCTtccttactaaCC	120_1	-23.93	66701
  120	TGCTTCCTTACTAACC	2-12-2	TGcttccttactaaCC	120_2	-20.10	66701
  121	CCCTTTGTAATCATCT	4-10-2	CCCTttgtaatcatCT	121_1	-23.44	66838
  122	TCCCTTTGTAATCATCT	2-13-2	TCcctttgtaatcatCT	122_1	-19.97	66838
  123	CTGCCATCAATACCAT	2-12-2	CTgccatcaataccAT	123_1	-19.14	68918
  124	TCACTGCCATCAATACC	2-13-2	TCactgccatcaataCC	124_1	-21.35	68920
  125	ATTCTTACTTTATTCCTCA	2-15-2	ATtcttactttattcctCA	125_1	-20.16	70033
  126	TCACTTTCCAGATATCA	4-11-2	TCACtttccagatatCA	126_1	-21.61	77567
  126	TCACTTTCCAGATATCA	2-13-2	TCactttccagatatCA	126_2	-18.65	77567
  127	TCCTTCAAATTCCACATAC	3-13-3	TCCttcaaattccacaTAC	127_1	-24.09	82053
  128	ACATGTCCCTTTATATT	4-11-2	ACATgtccctttataTT	128_1	-20.87	92323
  128	ACATGTCCCTTTATATT	2-13-2	ACatgtccctttataTT	128_2	-17.66	92323
  128	ACATGTCCCTTTATATT	3-12-2	ACAtgtccctttataTT	128_3	-19.13	92323
  128	ACATGTCCCTTTATATT	3-11-3	ACAtgtccctttatATT	128_4	-20.03	92323
  129	ACATGTCCCTTTATAT	3-10-3	ACAtgtccctttaTAT	129_1	-20.11	92324
  129	ACATGTCCCTTTATAT	2-12-2	ACatgtccctttatAT	129_2	-16.74	92324
  130	CCAAGAAAGGAGCAAGCT	3-12-3	CCAagaaaggagcaaGCT	130_1	-25.26	97146
  131	TCCAAGAAAGGAGCAAGC	3-12-3	TCCaagaaaggagcaAGC	131_1	-24.12	97147
  132	CTCATCCCTCCAAGAAA	4-11-2	CTCAtccctccaagaAA	132_1	-22.58	97156
  132	CTCATCCCTCCAAGAAA	2-13-2	CTcatccctccaagaAA	132_2	-19.83	97156
  132	CTCATCCCTCCAAGAAA	3-12-2	CTCatccctccaagaAA	132_3	-21.11	97156
  133	TCATCCCTCCAAGAAA	4-10-2	TCATccctccaagaAA	133_1	-20.41	97156
  133	TCATCCCTCCAAGAAA	2-12-2	TCatccctccaagaAA	133_2	-17.63	97156
  133	TCATCCCTCCAAGAAA	3-11-2	TCAtccctccaagaAA	133_3	-19.09	97156
  133	TCATCCCTCCAAGAAA	3-10-3	TCAtccctccaagAAA	133_4	-19.81	97156
  134	CACCTCCCTATTACATAAA	4-13-2	CACCtccctattacataAA	134_1	-24.18	100018
  134	CACCTCCCTATTACATAAA	2-15-2	CAcctccctattacataAA	134_2	-20.51	100018
  135	CACCTCCCTATTACATAA	4-12-2	CACCtccctattacatAA	135_1	-23.75	100019
  135	CACCTCCCTATTACATAA	2-14-2	CAcctccctattacatAA	135_2	-20.07	100019
  136	CCTCCCTATTACATAA	2-12-2	CCtccctattacatAA	136_1	-18.40	100019
  137	CTAAATCTTCCAATTCATA	2-15-2	CTaaatcttccaattcaTA	137_1	-18.12	106139
  138	TATCCCTTGATTATCCT	2-13-2	TAtcccttgattatcCT	138_1	-20.68	109406
  139	CCTCTTTGTCAAATACT	2-13-2	CCtctttgtcaaataCT	139_1	-19.30	110768
  140	CAGCTTATTTACCTCTT	2-13-2	CAgcttatttacctcTT	140_1	-19.30	114828
  141	ACTCTTTACCTCTAACACT	4-13-2	ACTCtttacctctaacaCT	141_1	-24.26	117468
  142	TTACTCTTTACCTCTAACAC	3-14-3	TTActctttacctctaaCAC	142_1	-23.23	117469
  143	CCAACCTAATACCTTAATA	2-15-2	CCaacctaataccttaaTA	143_1	-20.27	118639
  144	TACCAACCTAATACCTTAA	2-15-2	TAccaacctaataccttAA	144_1	-18.32	118641
  145	CCAATACCCACAAACC	3-10-3	CCAatacccacaaACC	145_1	-23.17	124162
  145	CCAATACCCACAAACC	2-12-2	CCaatacccacaaaCC	145_2	-20.85	124162
  146	CCATTATTCTACTTTGT	3-11-3	CCAttattctacttTGT	146_1	-21.79	125501
  146	CCATTATTCTACTTTGT	2-13-2	CCattattctactttGT	146_2	-18.63	125501
  147	CATTTCCTTATCTTCACA	2-14-2	CAtttccttatcttcaCA	147_1	-20.39	125529
  148	TCATTTCCTTATCTTCACA	4-13-2	TCATttccttatcttcaCA	148_1	-24.13	125529
  149	AATAATTCCTCATTTCCT	2-14-2	AAtaattcctcatttcCT	149_1	-18.01	125539
  150	ACAATAATTCCTCATTTCC	3-13-3	ACAataattcctcattTCC	150_1	-22.71	125540
  150	ACAATAATTCCTCATTTCC	2-15-2	ACaataattcctcatttCC	150_2	-20.23	125540
  151	TATTGAACCAATTCTA	3-10-3	TATtgaaccaattCTA	151_1	-16.93	4806
  152	CATATTGAACCAATTC	4-10-2	CATAttgaaccaatTC	152_1	-16.32	4808
  153	TCATATTGAACCAATT	4-10-2	TCATattgaaccaaTT	153_1	-16.14	4809
  154	CATCATATTGAACCAA	2-10-4	CAtcatattgaaCCAA	154_1	-17.65	4811
  155	TCATCATATTGAACCA	3-10-3	TCAtcatattgaaCCA	155_1	-19.40	4812
  156	CACAATCAACAACAAATA	4-12-2	CACAatcaacaacaaaTA	156_1	-16.16	4972
  157	TACACAATCAACAACAAAT	4-13-2	TACAcaatcaacaacaaAT	157_1	-16.76	4973
  158	CTGTACACAATCAACA	4-10-2	CTGTacacaatcaaCA	158_1	-19.05	4979
  159	CACTAATAATTCACTTT	4-11-2	CACTaataattcactTT	159_1	-16.39	5058
  160	CAACATTATTGACACT	2-10-4	CAacattattgaCACT	160_1	-17.17	5071
  161	AAACTTTCCCAACATTAT	2-12-4	AAactttcccaacaTTAT	161_1	-18.69	5078
  162	TCCTATATTCTCTTAAA	4-11-2	TCCTatattctcttaAA	162_1	-18.58	5094
  163	TTTCCTATATTCTCTTA	4-11-2	TTTCctatattctctTA	163_1	-18.69	5096
  164	CAAGTTTCCTATATTCT	4-11-2	CAAGtttcctatattCT	164_1	-19.97	5100
  165	CAAGTTTCCTATATTC	4-10-2	CAAGtttcctatatTC	165_1	-17.47	5101
  166	CATTCTATCTGCCAAA	2-10-4	CAttctatctgcCAAA	166_1	-18.36	5218
  167	CCATTCTATCTGCCAAA	2-11-4	CCattctatctgcCAAA	167_1	-22.08	5218
  168	TATAGCCATTCTATCT	4-10-2	TATAgccattctatCT	168_1	-20.63	5224
  169	TTATAGCCATTCTATCT	4-11-2	TTATagccattctatCT	169_1	-20.82	5224
  169	TTATAGCCATTCTATCT	1-10-3-1-2	TtatagccattCTAtCT	169_2	-20.51	5224
  169	TTATAGCCATTCTATCT	2-9-1-2-3	TTatagccattCtaTCT	169_3	-20.12	5224
  169	TTATAGCCATTCTATCT	1-1-1-8-2-1-3	TtAtagccattCTaTCT	169_4	-20.59	5224
  169	TTATAGCCATTCTATCT	1-3-1-6-2-2-2	TtatAgccattCTatCT	169_5	-19.97	5224
  169	TTATAGCCATTCTATCT	3-8-1-3-2	TTAtagccattCtatCT	169_6	-20.13	5224
  169	TTATAGCCATTCTATCT	1-10-2-2-2	TtatagccattCTatCT	169_7	-19.37	5224
  169	TTATAGCCATTCTATCT	2-9-1-1-4	TTatagccattCtATCT	169_8	-21.02	5224
  169	TTATAGCCATTCTATCT	1-1-1-8-1-1-4	TtAtagccattCtATCT	169_9	-19.88	5224
  169	TTATAGCCATTCTATCT	1-2-1-7-1-1-4	TtaTagccattCtATCT	169_10	-20.65	5224
  169	TTATAGCCATTCTATCT	1-3-1-6-1-1-4	TtatAgccattCtATCT	169_11	-20.38	5224
  169	TTATAGCCATTCTATCT	1-10-1-1-4	TtatagccattCtATCT	169_12	-19.78	5224
  169	TTATAGCCATTCTATCT	3-8-1-1-1-1-2	TTAtagccattCtAtCT	169_13	-20.22	5224
  169	TTATAGCCATTCTATCT	2-1-1-7-1-1-1-1-2	TTaTagccattCtAtCT	169_14	-19.96	5224
  169	TTATAGCCATTCTATCT	2-2-1-6-1-1-1-1-2	TTatAgccattCtAtCT	169_15	-19.69	5224
  169	TTATAGCCATTCTATCT	2-9-1-1-1-1-2	TTatagccattCtAtCT	169_16	-19.09	5224
  169	TTATAGCCATTCTATCT	1-2-2-6-1-1-1-1-2	TtaTAgccattCtAtCT	169_17	-20.35	5224
  169	TTATAGCCATTCTATCT	1-2-1-7-1-1-1-1-2	TtaTagccattCtAtCT	169_18	-18.72	5224
  169	TTATAGCCATTCTATCT	1-3-1-6-1-1-1-1-2	TtatAgccattCtAtCT	169_19	-18.45	5224
  169	TTATAGCCATTCTATCT	2-2-1-6-1-2-3	TTatAgccattCtaTCT	169_20	-20.71	5224
  169	TTATAGCCATTCTATCT	1-1-2-7-1-2-3	TtATagccattCtaTCT	169_21	-20.65	5224
  169	TTATAGCCATTCTATCT	1-1-1-1-1-6-1-2-3	TtAtAgccattCtaTCT	169_22	-19.57	5224
  169	TTATAGCCATTCTATCT	1-1-1-8-1-2-3	TtAtagccattCtaTCT	169_23	-18.98	5224
  169	TTATAGCCATTCTATCT	4-7-1-3-2	TTATagccattCtatCT	169_24	-21.80	5224
  169	TTATAGCCATTCTATCT	3-1-1-6-1-3-2	TTAtAgccattCtatCT	169_25	-20.72	5224
  169	TTATAGCCATTCTATCT	2-1-1-7-1-3-2	TTaTagccattCtatCT	169_26	-19.86	5224
  169	TTATAGCCATTCTATCT	2-2-1-6-1-3-2	TTatAgccattCtatCT	169_27	-19.59	5224
  169	TTATAGCCATTCTATCT	2-9-1-3-2	TTatagccattCtatCT	169_28	-18.99	5224
  169	TTATAGCCATTCTATCT	1-1-3-6-1-3-2	TtATAgccattCtatCT	169_29	-21.16	5224
  169	TTATAGCCATTCTATCT	1-1-2-7-1-3-2	TtATagccattCtatCT	169_30	-19.53	5224
  169	TTATAGCCATTCTATCT	1-1-1-1-1-6-1-3-2	TtAtAgccattCtatCT	169_31	-18.45	5224
  169	TTATAGCCATTCTATCT	1-2-2-6-1-3-2	TtaTAgccattCtatCT	169_32	-20.25	5224
  169	TTATAGCCATTCTATCT	1-2-1-7-1-3-2	TtaTagccattCtatCT	169_33	-18.62	5224
  169	TTATAGCCATTCTATCT	1-3-1-6-1-3-2	TtatAgccattCtatCT	169_34	-18.35	5224
  169	TTATAGCCATTCTATCT	1-1-1-9-5	TtAtagccattcTATCT	169_35	-20.88	5224
  169	TTATAGCCATTCTATCT	2-10-2-1-2	TTatagccattcTAtCT	169_36	-20.09	5224
  169	TTATAGCCATTCTATCT	1-1-1-9-2-1-2	TtAtagccattcTAtCT	169_37	-18.95	5224
  169	TTATAGCCATTCTATCT	1-2-1-8-2-1-2	TtaTagccattcTAtCT	169_38	-19.72	5224
  169	TTATAGCCATTCTATCT	1-3-1-7-2-1-2	TtatAgccattcTAtCT	169_39	-19.44	5224
  169	TTATAGCCATTCTATCT	1-11-2-1-2	TtatagccattcTAtCT	169_40	-18.85	5224
  169	TTATAGCCATTCTATCT	3-9-1-1-3	TTAtagccattcTaTCT	169_41	-21.21	5224
  169	TTATAGCCATTCTATCT	1-1-1-9-1-1-3	TtAtagccattcTaTCT	169_42	-18.94	5224
  169	TTATAGCCATTCTATCT	3-9-1-2-2	TTAtagccattcTatCT	169_43	-20.09	5224
  169	TTATAGCCATTCTATCT	1-2-1-8-1-2-2	TtaTagccattcTatCT	169_44	-18.58	5224
  169	TTATAGCCATTCTATCT	1-3-1-7-1-2-2	TtatAgccattcTatCT	169_45	-18.31	5224
  169	TTATAGCCATTCTATCT	1-1-1-10-4	TtAtagccattctATCT	169_46	-18.90	5224
  169	TTATAGCCATTCTATCT	3-10-1-1-2	TTAtagccattctAtCT	169_47	-19.24	5224
  169	TTATAGCCATTCTATCT	2-11-1-1-2	TTatagccattctAtCT	169_48	-18.11	5224
  169	TTATAGCCATTCTATCT	1-2-2-8-1-1-2	TtaTAgccattctAtCT	169_49	-19.37	5224
  169	TTATAGCCATTCTATCT	3-1-1-10-2	TTAtAgccattctatCT	169_50	-19.74	5224
  169	TTATAGCCATTCTATCT	3-12-2	TTAtagccattctatCT	169_51	-19.15	5224
  169	TTATAGCCATTCTATCT	2-1-2-10-2	TTaTAgccattctatCT	169_52	-20.51	5224
  169	TTATAGCCATTCTATCT	2-1-1-11-2	TTaTagccattctatCT	169_53	-18.88	5224
  169	TTATAGCCATTCTATCT	2-2-1-10-2	TTatAgccattctatCT	169_54	-18.61	5224
  169	TTATAGCCATTCTATCT	2-13-2	TTatagccattctatCT	169_55	-18.02	5224
  169	TTATAGCCATTCTATCT	1-1-3-10-2	TtATAgccattctatCT	169_56	-20.18	5224
  169	TTATAGCCATTCTATCT	1-1-2-11-2	TtATagccattctatCT	169_57	-18.55	5224
  169	TTATAGCCATTCTATCT	2-9-3-1-2	TTatagccattCTAtCT	169_58	-21.75	5224
  169	TTATAGCCATTCTATCT	1-1-1-8-2-2-2	TtAtagccattCTatCT	169_59	-19.47	5224
  169	TTATAGCCATTCTATCT	1-2-2-6-2-2-2	TtaTAgccattCTatCT	169_60	-21.87	5224
  169	TTATAGCCATTCTATCT	1-1-3-6-1-1-1-1-2	TtATAgccattCtAtCT	169_61	-21.25	5224
  169	TTATAGCCATTCTATCT	3-8-1-2-3	TTAtagccattCtaTCT	169_62	-21.25	5224
  170	ATTTAAATTTCCAAACATT	2-13-4	ATttaaatttccaaaCATT	170_1	-16.82	5427
  171	GCTAATTTAAATTTCC	4-10-2	GCTAatttaaatttCC	171_1	-18.50	5434
  172	ATCAATATCTTCTCAC	3-10-3	ATCaatatcttctCAC	172_1	-17.10	5785
  173	TATCAATATCTTCTCA	2-10-4	TAtcaatatcttCTCA	173_1	-17.55	5786
  174	CTACAAATTCAATTTACT	2-12-4	CTacaaattcaattTACT	174_1	-17.38	6341
  175	TCTTACTCTGACTTTCCA	2-14-2	TCttactctgactttcCA	175_1	-21.47	6694
  176	TCTTACTCTGACTTTCC	2-12-3	TCttactctgacttTCC	176_1	-21.53	6695
  177	AAATTTCCAAACCTTTC	2-11-4	AAatttccaaaccTTTC	177_1	-16.30	6958
  178	CTTCTTGTTTATCCCAA	2-11-4	CTtcttgtttatcCCAA	178_1	-22.77	7159
  179	TTCTTGTTTATCCCAA	2-10-4	TTcttgtttatcCCAA	179_1	-20.17	7159
  180	ATGCTTCTAACTAACA	4-10-2	ATGCttctaactaaCA	180_1	-19.21	7720
  181	CTTTAATGCTTCTAACT	4-11-2	CTTTaatgcttctaaCT	181_1	-18.49	7724
  182	CCTTTAATGCTTCTAAC	2-11-4	CCtttaatgcttcTAAC	182_1	-20.06	7725
  183	CTTTAATGCTTCTAAC	2-10-4	CTttaatgcttcTAAC	183_1	-16.07	7725
  184	TTCCTTTAATGCTTCTA	4-11-2	TTCCtttaatgcttcTA	184_1	-21.59	7727
  185	TATACCTTTCTTTAACCCT	2-15-2	TAtacctttctttaaccCT	185_1	-22.03	8117
  186	ATACCTTTCTTTAACCC	4-11-2	ATACctttctttaacCC	186_1	-22.68	8118
  187	TTATACCTTTCTTTAACC	4-12-2	TTATacctttctttaaCC	187_1	-21.52	8119
  188	TTTATACCTTTCTTTAAC	2-12-4	TTtatacctttcttTAAC	188_1	-17.01	8120
  189	TCAAGAATTCTCTCCTT	2-11-4	TCaagaattctctCCTT	189_1	-21.29	8571
  190	TTCAAGAATTCTCTCC	2-10-4	TTcaagaattctCTCC	190_1	-19.38	8573
  191	CTTCAAGAATTCTCTC	2-10-4	CTtcaagaattcTCTC	191_1	-18.00	8574
  192	TCTTCAAGAATTCTCT	2-10-4	TCttcaagaattCTCT	192_1	-18.46	8575
  193	ATCTTCAAGAATTCTC	3-10-3	ATCttcaagaattCTC	193_1	-17.04	8576
  194	TTTCTTACTATCTTCA	4-10-2	TTTCttactatcttCA	194_1	-17.47	8585
  195	CCTTTAGCATTTCTATT	2-11-4	CCtttagcatttcTATT	195_1	-21.72	8819
  196	TCCTTTAGCATTTCTAT	3-11-3	TCCtttagcatttcTAT	196_1	-22.39	8820
  197	GTTCTCTTTATTTCTTCT	2-12-4	GTtctctttatttcTTCT	197_1	-21.76	8887
  198	TTTACTGTCAACTCCT	2-10-4	TTtactgtcaacTCCT	198_1	-20.83	9150
  199	TTTCCAATGAATCTAT	2-10-4	TTtccaatgaatCTAT	199_1	-16.61	9201
  200	CCTTTCCAATGAATCTA	2-11-4	CCtttccaatgaaTCTA	200_1	-22.34	9202
  201	CTTTCCAATGAATCTA	2-10-4	CTttccaatgaaTCTA	201_1	-18.34	9202
  202	CCTTTCCAATGAATCT	3-10-3	CCTttccaatgaaTCT	202_1	-21.30	9203
  203	TTATACCCTTTCCAAT	2-10-4	TTataccctttcCAAT	203_1	-19.61	9209
  204	GTTTATACCCTTTCCAA	3-11-3	GTTtataccctttcCAA	204_1	-21.88	9210
  205	TTTATACCCTTTCCAA	2-10-4	TTtataccctttCCAA	205_1	-20.50	9210
  206	GTTTATACCCTTTCCA	2-11-3	GTttataccctttCCA	206_1	-22.69	9211
  207	TGTTTATACCCTTTCCA	3-12-2	TGTttataccctttcCA	207_1	-22.80	9211
  208	ACTGTTTATACCCTTTCC	2-14-2	ACtgtttataccctttCC	208_1	-22.96	9212
  208	ACTGTTTATACCCTTTCC	1-11-1-3-2	ActgtttataccCtttCC	208_2	-22.45	9212
  208	ACTGTTTATACCCTTTCC	1-2-1-10-1-1-2	ActGtttataccctTtCC	208_3	-22.17	9212
  208	ACTGTTTATACCCTTTCC	1-2-1-1-1-10-2	ActGtTtataccctttCC	208_4	-22.17	9212
  208	ACTGTTTATACCCTTTCC	1-2-1-12-2	ActGtttataccctttCC	208_5	-21.87	9212
  208	ACTGTTTATACCCTTTCC	1-3-1-11-2	ActgTttataccctttCC	208_6	-22.22	9212
  208	ACTGTTTATACCCTTTCC	1-15-2	ActgtttataccctttCC	208_7	-21.56	9212
  209	ACTGTTTATACCCTTTC	4-11-2	ACTGtttatacccttTC	209_1	-21.65	9213
  209	ACTGTTTATACCCTTTC	1-11-1-2-2	ActgtttataccCttTC	209_2	-18.25	9213
  209	ACTGTTTATACCCTTTC	1-1-1-8-1-1-1-1-2	AcTgtttatacCcTtTC	209_3	-19.56	9213
  209	ACTGTTTATACCCTTTC	1-2-1-9-4	ActGtttatacccTTTC	209_4	-19.51	9213
  209	ACTGTTTATACCCTTTC	1-3-1-6-1-2-3	ActgTttatacCctTTC	209_5	-19.51	9213
  209	ACTGTTTATACCCTTTC	2-9-1-3-2	ACtgtttatacCcttTC	209_6	-19.43	9213
  209	ACTGTTTATACCCTTTC	1-2-1-7-1-3-2	ActGtttatacCcttTC	209_7	-18.35	9213
  209	ACTGTTTATACCCTTTC	1-3-1-8-1-1-2	ActgTttatacccTtTC	209_8	-18.53	9213
  209	ACTGTTTATACCCTTTC	1-11-1-1-3	ActgtttataccCtTTC	209_9	-19.06	9213
  209	ACTGTTTATACCCTTTC	2-10-1-2-2	ACtgtttataccCttTC	209_10	-19.64	9213
  210	AACTGTTTATACCCTTT	4-11-2	AACTgtttataccctTT	210_1	-19.51	9214
  211	TATGACTCCAATAATC	3-10-3	TATgactccaataATC	211_1	-16.57	10832
  212	CTCCTTTATGACTCCAA	4-11-2	CTCCtttatgactccAA	212_1	-22.74	10837
  213	CTCCTTTATGACTCCA	3-11-2	CTCctttatgactcCA	213_1	-21.50	10838
  214	CCATTATTTCTTAAATA	4-11-2	CCATtatttcttaaaTA	214_1	-17.56	10877
  215	ATTTCATATTACTAACTA	2-12-4	ATttcatattactaACTA	215_1	-16.64	11434
  216	CATTTCATATTACTAACT	3-12-3	CATttcatattactaACT	216_1	-17.70	11435
  217	TCATTTCATATTACTAAC	4-12-2	TCATttcatattactaAC	217_1	-16.72	11436
  218	ATCATTTCATATTACTA	3-11-3	ATCatttcatattaCTA	218_1	-17.23	11438
  219	TTATCATTTCATATTACT	4-12-2	TTATcatttcatattaCT	219_1	-17.77	11439
  220	TGTACTTTCCTTTACCA	2-13-2	TGtactttcctttacCA	220_1	-20.37	11464
  221	TATACACCATCATTATA	4-11-2	TATAcaccatcattaTA	221_1	-18.48	11507
  222	TTATACACCATCATTAT	3-11-3	TTAtacaccatcatTAT	222_1	-17.83	11508
  223	TATTTATACACCATCAT	3-11-3	TATttatacaccatCAT	223_1	-18.54	11511
  224	TTATTTATACACCATC	2-10-4	TTatttatacacCATC	224_1	-16.60	11513
  225	AATTATTTATACACCAT	2-11-4	AAttatttatacaCCAT	225_1	-16.82	11514
  226	CATGACACTTACATAA	3-10-3	CATgacacttacaTAA	226_1	-16.26	11736
  227	AGTTCACTACTATTAC	3-10-3	AGTtcactactatTAC	227_1	-17.55	12361
  228	ATAAGCTTACCTCATA	2-10-4	ATaagcttacctCATA	228_1	-19.32	12794
  229	TATAAGCTTACCTCAT	3-10-3	TATaagcttacctCAT	229_1	-19.32	12795
  230	ATATAAGCTTACCTCA	4-10-2	ATATaagcttacctCA	230_1	-19.32	12796
  231	CTTCCCTTTGATAACAT	3-11-3	CTTccctttgataaCAT	231_1	-21.19	12894
  232	TTCCCTTTGATAACAT	4-10-2	TTCCctttgataacAT	232_1	-19.27	12894
  233	CCTTCCCTTTGATAACA	2-12-3	CCttccctttgataACA	233_1	-23.06	12895
  234	CTTCCCTTTGATAACA	4-10-2	CTTCcctttgataaCA	234_1	-20.51	12895
  235	CCTTCCCTTTGATAAC	3-11-2	CCTtccctttgataAC	235_1	-20.96	12896
  236	TTGATTCAATTCCCTTA	2-11-4	TTgattcaattccCTTA	236_1	-20.48	13223
  236	TTGATTCAATTCCCTTA	2-9-1-1-1-1-2	TTgattcaattCcCtTA	236_2	-19.54	13223
  236	TTGATTCAATTCCCTTA	2-10-1-1-3	TTgattcaattcCcTTA	236_3	-19.59	13223
  236	TTGATTCAATTCCCTTA	2-1-1-8-1-2-2	TTgAttcaattcCctTA	236_4	-19.06	13223
  236	TTGATTCAATTCCCTTA	2-2-1-7-1-2-2	TTgaTtcaattcCctTA	236_5	-19.00	13223
  236	TTGATTCAATTCCCTTA	2-9-1-3-2	TTgattcaattCcctTA	236_6	-18.65	13223
  236	TTGATTCAATTCCCTTA	1-2-2-6-2-2-2	TtgATtcaattCCctTA	236_7	-21.37	13223
  236	TTGATTCAATTCCCTTA	2-1-1-7-1-1-1-1-2	TTgAttcaattCcCtTA	236_8	-20.04	13223
  236	TTGATTCAATTCCCTTA	1-1-2-7-1-1-1-1-2	TtGAttcaattCcCtTA	236_9	-20.10	13223
  236	TTGATTCAATTCCCTTA	1-2-1-9-4	TtgAttcaattccCTTA	236_10	-19.67	13223
  236	TTGATTCAATTCCCTTA	1-3-1-6-1-1-1-1-2	TtgaTtcaattCcCtTA	236_11	-18.67	13223
  236	TTGATTCAATTCCCTTA	2-10-1-2-2	TTgattcaattcCctTA	236_12	-18.56	13223
  236	TTGATTCAATTCCCTTA	1-2-2-7-2-1-2	TtgATtcaattcCCtTA	236_13	-21.49	13223
  236	TTGATTCAATTCCCTTA	1-1-2-8-1-2-2	TtGAttcaattcCctTA	236_14	-19.13	13223
  236	TTGATTCAATTCCCTTA	2-11-1-1-2	TTgattcaattccCtTA	236_15	-18.77	13223
  236	TTGATTCAATTCCCTTA	1-1-1-1-1-8-1-1-2	TtGaTtcaattccCtTA	236_16	-18.07	13223
  236	TTGATTCAATTCCCTTA	1-1-2-7-2-2-2	TtGAttcaattCCctTA	236_17	-21.50	13223
  236	TTGATTCAATTCCCTTA	1-2-1-7-1-1-4	TtgAttcaattCcCTTA	236_18	-20.44	13223
  236	TTGATTCAATTCCCTTA	3-8-1-1-1-1-2	TTGattcaattCcCtTA	236_19	-20.60	13223
  236	TTGATTCAATTCCCTTA	2-2-1-6-1-3-2	TTgaTtcaattCcctTA	236_20	-19.09	13223
  236	TTGATTCAATTCCCTTA	2-2-1-7-2-1-2	TTgaTtcaattcCCtTA	236_21	-21.49	13223
  237	ATTGATTCAATTCCCTT	2-11-4	ATtgattcaattcCCTT	237_1	-21.28	13224
  237	ATTGATTCAATTCCCTT	3-8-3-1-2	ATTgattcaatTCCcTT	237_2	-22.78	13224
  237	ATTGATTCAATTCCCTT	1-1-1-8-3-1-2	AtTgattcaatTCCcTT	237_3	-21.02	13224
  237	ATTGATTCAATTCCCTT	1-2-1-8-2-1-2	AttGattcaattCCcTT	237_4	-19.40	13224
  237	ATTGATTCAATTCCCTT	1-3-1-7-2-1-2	AttgAttcaattCCcTT	237_5	-19.74	13224
  237	ATTGATTCAATTCCCTT	1-2-1-7-2-1-3	AttGattcaatTCcCTT	237_6	-19.67	13224
  237	ATTGATTCAATTCCCTT	2-2-1-7-1-1-3	ATtgAttcaattCcCTT	237_7	-20.27	13224
  237	ATTGATTCAATTCCCTT	1-1-1-9-1-1-3	AtTgattcaattCcCTT	237_8	-19.32	13224
  237	ATTGATTCAATTCCCTT	1-3-1-7-1-1-3	AttgAttcaattCcCTT	237_9	-19.02	13224
  237	ATTGATTCAATTCCCTT	1-1-1-1-1-7-2-1-2	AtTgAttcaattCCcTT	237_10	-20.53	13224
  237	ATTGATTCAATTCCCTT	1-2-2-7-2-1-2	AttGAttcaattCCcTT	237_11	-21.11	13224
  237	ATTGATTCAATTCCCTT	1-2-1-8-1-1-3	AttGattcaattCcCTT	237_12	-18.68	13224
  237	ATTGATTCAATTCCCTT	1-1-2-8-1-2-2	AtTGattcaattCccTT	237_13	-18.81	13224
  237	ATTGATTCAATTCCCTT	3-10-1-1-2	ATTgattcaattcCcTT	237_14	-19.42	13224
  237	ATTGATTCAATTCCCTT	1-1-2-9-4	AtTGattcaattcCCTT	237_15	-21.89	13224
  237	ATTGATTCAATTCCCTT	2-2-1-8-1-1-2	ATtgAttcaattcCcTT	237_16	-18.61	13224
  237	ATTGATTCAATTCCCTT	1-2-2-6-3-1-2	AttGAttcaatTCCcTT	237_17	-22.09	13224
  237	ATTGATTCAATTCCCTT	1-1-1-8-2-1-3	AtTgattcaatTCcCTT	237_18	-20.30	13224
  237	ATTGATTCAATTCCCTT	1-1-1-9-2-1-2	AtTgattcaattCCcTT	237_19	-20.03	13224
  237	ATTGATTCAATTCCCTT	1-1-1-1-1-7-1-1-3	AtTgAttcaattCcCTT	237_20	-19.82	13224
  237	ATTGATTCAATTCCCTT	3-1-1-8-1-1-2	ATTgAttcaattcCcTT	237_21	-19.92	13224
  238	TTGATTCAATTCCCTT	2-10-4	TTgattcaattcCCTT	238_1	-20.52	13224
  239	TATTGATTCAATTCCCT	2-11-4	TAttgattcaattCCCT	239_1	-22.82	13225
  239	TATTGATTCAATTCCCT	3-9-2-1-2	TATtgattcaatTCcCT	239_2	-21.17	13225
  239	TATTGATTCAATTCCCT	2-9-1-1-1-1-2	TAttgattcaaTtCcCT	239_3	-19.37	13225
  239	TATTGATTCAATTCCCT	1-1-2-7-3-1-2	TaTTgattcaaTTCcCT	239_4	-21.49	13225
  239	TATTGATTCAATTCCCT	1-3-1-6-3-1-2	TattGattcaaTTCcCT	239_5	-19.90	13225
  239	TATTGATTCAATTCCCT	2-9-1-2-3	TAttgattcaaTtcCCT	239_6	-20.89	13225
  239	TATTGATTCAATTCCCT	1-10-1-2-3	TattgattcaaTtcCCT	239_7	-19.76	13225
  239	TATTGATTCAATTCCCT	1-1-1-1-1-8-1-1-2	TaTtGattcaattCcCT	239_8	-18.41	13225
  239	TATTGATTCAATTCCCT	1-2-2-8-1-1-2	TatTGattcaattCcCT	239_9	-19.66	13225
  239	TATTGATTCAATTCCCT	1-2-1-9-1-1-2	TatTgattcaattCcCT	239_10	-18.60	13225
  239	TATTGATTCAATTCCCT	2-2-1-10-2	TAttGattcaattccCT	239_11	-18.33	13225
  239	TATTGATTCAATTCCCT	1-12-4	TattgattcaattCCCT	239_12	-21.69	13225
  239	TATTGATTCAATTCCCT	2-1-1-9-1-1-2	TAtTgattcaattCcCT	239_13	-19.73	13225
  239	TATTGATTCAATTCCCT	2-12-3	TAttgattcaattcCCT	239_14	-20.45	13225
  239	TATTGATTCAATTCCCT	1-2-1-10-3	TatTgattcaattcCCT	239_15	-20.11	13225
  239	TATTGATTCAATTCCCT	1-1-3-10-2	TaTTGattcaattccCT	239_16	-19.84	13225
  239	TATTGATTCAATTCCCT	1-1-1-1-1-6-3-1-2	TaTtGattcaaTTCcCT	239_17	-20.34	13225
  239	TATTGATTCAATTCCCT	2-2-1-6-1-1-1-1-2	TAttGattcaaTtCcCT	239_18	-19.54	13225
  239	TATTGATTCAATTCCCT	2-1-1-8-2-1-2	TAtTgattcaatTCcCT	239_19	-20.72	13225
  239	TATTGATTCAATTCCCT	1-1-2-9-1-1-2	TaTTgattcaattCcCT	239_20	-19.55	13225
  239	TATTGATTCAATTCCCT	2-1-1-10-3	TAtTgattcaattcCCT	239_21	-21.24	13225
  240	TATTGATTCAATTCCC	3-10-3	TATtgattcaattCCC	240_1	-20.58	13226
  241	GCACATTCTTTCTATAC	3-11-3	GCAcattctttctaTAC	241_1	-21.17	15115
  241	GCACATTCTTTCTATAC	1-1-3-6-2-2-2	GcACAttctttCTatAC	241_2	-20.68	15115
  241	GCACATTCTTTCTATAC	1-1-1-1-1-6-1-2-3	GcAcAttctttCtaTAC	241_3	-18.46	15115
  241	GCACATTCTTTCTATAC	1-1-2-7-1-2-3	GcACattctttCtaTAC	241_4	-19.49	15115
  241	GCACATTCTTTCTATAC	2-9-1-3-2	GCacattctttCtatAC	241_5	-18.68	15115
  241	GCACATTCTTTCTATAC	1-1-3-8-4	GcACAttctttctATAC	241_6	-20.89	15115
  241	GCACATTCTTTCTATAC	2-2-1-9-3	GCacAttctttctaTAC	241_7	-19.66	15115
  241	GCACATTCTTTCTATAC	2-1-1-11-2	GCaCattctttctatAC	241_8	-18.39	15115
  241	GCACATTCTTTCTATAC	1-1-3-9-3	GcACAttctttctaTAC	241_9	-19.98	15115
  241	GCACATTCTTTCTATAC	3-12-2	GCAcattctttctatAC	241_10	-19.27	15115
  241	GCACATTCTTTCTATAC	1-1-1-1-1-6-1-1-4	GcAcAttctttCtATAC	241_11	-19.36	15115
  241	GCACATTCTTTCTATAC	3-8-1-1-1-1-2	GCAcattctttCtAtAC	241_12	-20.34	15115
  241	GCACATTCTTTCTATAC	2-1-1-7-1-2-3	GCaCattctttCtaTAC	241_13	-21.27	15115
  241	GCACATTCTTTCTATAC	1-2-2-8-4	GcaCAttctttctATAC	241_14	-20.33	15115
  241	GCACATTCTTTCTATAC	1-1-3-10-2	GcACAttctttctatAC	241_15	-18.08	15115
  242	GAATTTCAACTACTAT	2-10-4	GAatttcaactaCTAT	242_1	-16.13	15258
  243	CCATTTATTTCCATTTAT	3-12-3	CCAtttatttccattTAT	243_1	-21.92	15568
  244	TTTCCATTTATTTCCATTT	4-13-2	TTTCcatttatttccatTT	244_1	-20.93	15570
  244	TTTCCATTTATTTCCATTT	1-4-1-7-1-1-4	TttccAtttatttCcATTT	244_2	-20.48	15570
  244	TTTCCATTTATTTCCATTT	2-1-1-10-2-1-2	TTtCcatttatttcCAtTT	244_3	-21.47	15570
  244	TTTCCATTTATTTCCATTT	1-2-1-1-1-7-1-3-2	TttCcAtttatttCcatTT	244_4	-19.43	15570
  244	TTTCCATTTATTTCCATTT	2-2-2-11-2	TTtcCAtttatttccatTT	244_5	-20.70	15570
  245	CTTTCCATTTATTTCCAT	3-12-3	CTTtccatttatttcCAT	245_1	-22.31	15572
  246	TCTTTCCATTTATTTCCA	4-12-2	TCTTtccatttatttcCA	246_1	-22.74	15573
  247	ATCTTTCCATTTATTTCC	3-12-3	ATCtttccatttattTCC	247_1	-22.85	15574
  248	TTCCATGCAAACTTTA	4-10-2	TTCCatgcaaacttTA	248_1	-19.01	15722
  249	CAGTTTAAATTCACAC	3-10-3	CAGtttaaattcaCAC	249_1	-16.68	16597
  250	CTATTCCAGTTTAAAT	4-10-2	CTATtccagtttaaAT	250_1	-16.86	16603
  251	TGCAAATACCTCTTCA	4-10-2	TGCAaatacctcttCA	251_1	-21.49	16730
  252	CTAAATAGATTCCACT	2-10-4	CTaaatagattcCACT	252_1	-17.95	16849
  253	TATTGATATTTACTCT	2-10-4	TAttgatatttaCTCT	253_1	-16.32	17089
  254	CCTTAGTATTACAATT	4-10-2	CCTTagtattacaaTT	254_1	-17.43	17401
  255	CTATTCAATAAACTAAACA	4-13-2	CTATtcaataaactaaaCA	255_1	-16.45	24290
  256	CAGCTATTCAATAAAC	4-10-2	CAGCtattcaataaAC	256_1	-16.94	24296
  257	TATAGACCCAAACTAT	3-10-3	TATagacccaaacTAT	257_1	-18.15	24811
  258	TAATCCCATACATCTAT	2-11-4	TAatcccatacatCTAT	258_1	-20.45	25032
  259	ATAATCCCATACATCTA	3-11-3	ATAatcccatacatCTA	259_1	-20.45	25033
  260	ATCTCAACTACCATTT	4-10-2	ATCTcaactaccatTT	260_1	-18.14	25250
  261	AATCTCAACTACCATT	4-10-2	AATCtcaactaccaTT	261_1	-16.76	25251
  262	ACAACTTCTATCATAC	3-10-3	ACAacttctatcaTAC	262_1	-16.33	25718
  263	GAACAACTTCTATCAT	2-10-4	GAacaacttctaTCAT	263_1	-16.94	25720
  264	TGAACAACTTCTATCA	3-10-3	TGAacaacttctaTCA	264_1	-17.36	25721
  265	TACACAAATACTTAAATCA	4-13-2	TACAcaaatacttaaatCA	265_1	-16.93	26331
  266	TTAAGCTTTCACCTAT	2-10-4	TTaagctttcacCTAT	266_1	-19.36	27165
  267	AAACTCTTGCATCTACT	2-13-2	AAactcttgcatctaCT	267_1	-16.65	27248
  268	AAATTTCTCAACCTAAATTT	2-14-4	AAatttctcaacctaaATTT	268_1	-16.78	29330
  269	CCAACATAGATCCTCT	2-10-4	CCaacatagatcCTCT	269_1	-22.49	29635
  270	TCCAACATAGATCCTCT	2-11-4	TCcaacatagatcCTCT	270_1	-22.81	29635
  271	CTCCAACATAGATCCTC	3-11-3	CTCcaacatagatcCTC	271_1	-22.81	29636
  272	TCCAACATAGATCCTC	2-10-4	TCcaacatagatCCTC	272_1	-21.69	29636
  273	CTCCAACATAGATCCT	3-10-3	CTCcaacatagatCCT	273_1	-22.68	29637
  274	TCTCCAACATAGATCCT	4-11-2	TCTCcaacatagatcCT	274_1	-22.81	29637
  275	ATTCTCAATTGCACTT	4-10-2	ATTCtcaattgcacTT	275_1	-17.90	29661
  276	TATTCTCAATTGCACTT	4-11-2	TATTctcaattgcacTT	276_1	-18.54	29661
  277	TCACCTAATAGCACCA	2-10-4	TCacctaatagcACCA	277_1	-21.99	29684
  278	TTCACCTAATAGCACCA	2-11-4	TTcacctaatagcACCA	278_1	-22.53	29684
  279	CATTATTATTTAACCTT	2-11-4	CAttattatttaaCCTT	279_1	-17.83	30455
  280	ACATTATTATTTAACCT	3-11-3	ACAttattatttaaCCT	280_1	-18.05	30456
  281	TACATTATTATTTAACC	4-11-2	TACAttattatttaaCC	281_1	-16.80	30457
  282	CATTTACATTATTATTTAAC	2-14-4	CAtttacattattattTAAC	282_1	-16.44	30458
  283	CTCATTTACATTATTATT	4-12-2	CTCAtttacattattaTT	283_1	-17.33	30462
  284	TATCTCATTTACATTATT	4-12-2	TATCtcatttacattaTT	284_1	-17.62	30465
  285	ATCATTCTCAACAATTA	4-11-2	ATCAttctcaacaatTA	285_1	-17.04	30601
  285	ATCATTCTCAACAATTA	4-7-6	ATCAttctcaaCAATTA	285_2	-21.48	30601
  285	ATCATTCTCAACAATTA	1-1-3-6-6	AtCATtctcaaCAATTA	285_3	-20.80	30601
  285	ATCATTCTCAACAATTA	5-6-2-2-2	ATCATtctcaaCAatTA	285_4	-20.46	30601
  285	ATCATTCTCAACAATTA	4-7-1-1-4	ATCAttctcaaCaATTA	285_5	-19.80	30601
  285	ATCATTCTCAACAATTA	5-7-1-1-3	ATCATtctcaacAaTTA	285_6	-19.31	30601
  285	ATCATTCTCAACAATTA	5-6-3-1-2	ATCATtctcaaCAAtTA	285_7	-20.97	30601
  285	ATCATTCTCAACAATTA	4-7-2-1-3	ATCAttctcaaCAaTTA	285_8	-20.16	30601
  285	ATCATTCTCAACAATTA	5-6-1-1-4	ATCATtctcaaCaATTA	285_9	-21.05	30601
  285	ATCATTCTCAACAATTA	5-6-1-1-1-1-2	ATCATtctcaaCaAtTA	285_10	-19.29	30601
  285	ATCATTCTCAACAATTA	1-1-3-7-5	AtCATtctcaacAATTA	285_11	-18.70	30601
  286	AAGATCATTCTCAACA	4-10-2	AAGAtcattctcaaCA	286_1	-17.15	30605
  287	TCTCAAAGATCATTCTC	3-11-3	TCTcaaagatcattCTC	287_1	-19.02	30609
  288	TCTCAAAGATCATTCT	4-10-2	TCTCaaagatcattCT	288_1	-17.81	30610
  289	ACTTAATTATACTTCC	4-10-2	ACTTaattatacttCC	289_1	-17.28	30667
  290	TACACTTAATTATACTTC	2-12-4	TAcacttaattataCTTC	290_1	-16.87	30668
  291	TTACACTTAATTATACTT	3-12-3	TTAcacttaattataCTT	291_1	-16.20	30669
  292	TTTACACTTAATTATACT	2-12-4	TTtacacttaattaTACT	292_1	-16.23	30670
  293	CTATTTAATTTACACTT	3-11-3	CTAtttaatttacaCTT	293_1	-16.26	30679
  294	TATCTATTTAATTTACAC	3-12-3	TATctatttaatttaCAC	294_1	-16.06	30681
  295	TTTATCTATTTAATTTACA	4-13-2	TTTAtctatttaatttaCA	295_1	-16.34	30682
  296	CTCTGCTTATAACTTT	4-10-2	CTCTgcttataactTT	296_1	-18.51	30699
  297	CCTCTGCTTATAACTT	3-10-3	CCTctgcttataaCTT	297_1	-21.29	30700
  298	TCCTCTGCTTATAACTT	3-12-2	TCCtctgcttataacTT	298_1	-20.86	30700
  299	TCCTCTGCTTATAACT	3-11-2	TCCtctgcttataaCT	299_1	-20.70	30701
  300	TTCCTCTGCTTATAACT	3-12-2	TTCctctgcttataaCT	300_1	-20.03	30701
  301	TTTCCTCTGCTTATAAC	4-11-2	TTTCctctgcttataAC	301_1	-19.20	30702
  302	TACTATACTTTCCTCT	2-10-4	TActatactttcCTCT	302_1	-20.07	30711
  303	TTCTACTATACTTTCC	4-10-2	TTCTactatactttCC	303_1	-19.55	30714
  304	AGTTCTACTATACTTTC	4-11-2	AGTTctactatacttTC	304_1	-18.49	30715
  304	AGTTCTACTATACTTTC	1-10-6	AgttctactatACTTTC	304_2	-18.76	30715
  304	AGTTCTACTATACTTTC	1-1-2-7-1-1-4	AgTTctactatAcTTTC	304_3	-18.23	30715
  304	AGTTCTACTATACTTTC	3-8-2-2-2	AGTtctactatACttTC	304_4	-19.19	30715
  304	AGTTCTACTATACTTTC	2-2-1-6-1-1-4	AGttCtactatAcTTTC	304_5	-19.07	30715
  304	AGTTCTACTATACTTTC	1-2-2-8-4	AgtTCtactatacTTTC	304_6	-18.46	30715
  304	AGTTCTACTATACTTTC	3-10-1-1-2	AGTtctactatacTtTC	304_7	-18.12	30715
  304	AGTTCTACTATACTTTC	3-11-3	AGTtctactatactTTC	304_8	-18.42	30715
  304	AGTTCTACTATACTTTC	3-1-1-10-2	AGTtCtactatacttTC	304_9	-18.58	30715
  304	AGTTCTACTATACTTTC	2-1-2-10-2	AGtTCtactatacttTC	304_10	-18.02	30715
  304	AGTTCTACTATACTTTC	1-2-2-6-2-1-3	AgtTCtactatACtTTC	304_11	-19.02	30715
  304	AGTTCTACTATACTTTC	2-1-2-6-1-3-2	AGtTCtactatActtTC	304_12	-18.22	30715
  304	AGTTCTACTATACTTTC	2-2-1-7-2-1-2	AGttCtactataCTtTC	304_13	-19.22	30715
  304	AGTTCTACTATACTTTC	3-1-1-7-1-1-3	AGTtCtactataCtTTC	304_14	-20.39	30715
  304	AGTTCTACTATACTTTC	1-1-1-1-1-8-4	AgTtCtactatacTTTC	304_15	-18.13	30715
  305	GTTCTACTATACTTTC	4-10-2	GTTCtactatacttTC	305_1	-17.48	30715
  306	CATTATATTTAAACTATCA	4-13-2	CATTatatttaaactatCA	306_1	-16.93	31630
  307	CACATTATATTTAAACTAT	2-13-4	CAcattatatttaaaCTAT	307_1	-17.11	31632
  308	ACACATTATATTTAAACTA	3-13-3	ACAcattatatttaaaCTA	308_1	-17.09	31633
  309	ACCACCTAAGACCTCAA	2-11-4	ACcacctaagaccTCAA	309_1	-22.49	32755
  310	CCACCTAAGACCTCAA	2-10-4	CCacctaagaccTCAA	310_1	-22.63	32755
  311	ACCACCTAAGACCTCA	2-11-3	ACcacctaagaccTCA	311_1	-21.74	32756
  312	ACCTTAAGTAACATTT	4-10-2	ACCTtaagtaacatTT	312_1	-16.82	33366
  313	CACCTTAAGTAACATT	4-10-2	CACCttaagtaacaTT	313_1	-18.05	33367
  314	CCACCTTAAGTAACAT	3-10-3	CCAccttaagtaaCAT	314_1	-20.70	33368
  315	ACCACCTTAAGTAACA	4-10-2	ACCAccttaagtaaCA	315_1	-20.68	33369
  316	TTATTAACCACCTTAA	3-10-3	TTAttaaccacctTAA	316_1	-16.19	33375
  317	CATTATTAACCACCTT	2-10-4	CAttattaaccaCCTT	317_1	-19.92	33377
  318	ACATTATTAACCACCT	3-10-3	ACAttattaaccaCCT	318_1	-20.14	33378
  319	ACCAATTATACTTACAA	3-11-3	ACCaattatacttaCAA	319_1	-17.16	36606
  320	AACCAATTATACTTACA	4-11-2	AACCaattatacttaCA	320_1	-17.16	36607
  321	CAAATACAGATTATCC	2-10-4	CAaatacagattATCC	321_1	-16.44	38092
  322	TTTACATTCCCATCATC	2-11-4	TTtacattcccatCATC	322_1	-21.08	38297
  323	CACACCTATTATATAAT	4-11-2	CACAcctattatataAT	323_1	-17.02	39173
  324	TCACACCTATTATATAA	3-11-3	TCAcacctattataTAA	324_1	-17.02	39174
  325	CTTCACACCTATTATATA	2-12-4	CTtcacacctattaTATA	325_1	-20.65	39175
  326	ACTTCACACCTATTATAT	3-12-3	ACTtcacacctattaTAT	326_1	-20.46	39176
  327	GCTCACACTAATTATT	2-10-4	GCtcacactaatTATT	327_1	-18.72	39228
  328	ATGCTCACACTAATTA	4-10-2	ATGCtcacactaatTA	328_1	-19.38	39230
  329	AATGCTCACACTAATT	4-10-2	AATGctcacactaaTT	329_1	-16.21	39231
  330	AAACTGTACACCTACT	2-10-4	AAactgtacaccTACT	330_1	-17.99	39563
  331	GTTTCCATCTACTATTA	2-11-4	GTttccatctactATTA	331_1	-19.78	39808
  332	TTTCCATCTACTATTA	4-10-2	TTTCcatctactatTA	332_1	-17.25	39808
  333	TGACATAACCATATAC	3-10-3	TGAcataaccataTAC	333_1	-16.63	39931
  334	GCTCCCAAACAACTAA	2-12-2	GCtcccaaacaactAA	334_1	-17.55	41114
  335	CCTCAATACTCTACTT	4-10-2	CCTCaatactctacTT	335_1	-20.30	41444
  336	GACCTCAATACTCTACT	3-11-3	GACctcaatactctACT	336_1	-21.01	41445
  337	GACCTCAATACTCTAC	4-10-2	GACCtcaatactctAC	337_1	-20.02	41446
  338	TACTAAACATACACATA	4-11-2	TACTaaacatacacaTA	338_1	-16.12	41725
  339	CTACTAAACATACACAT	3-11-3	CTActaaacatacaCAT	339_1	-17.31	41726
  340	TTCTACTAAACATACAC	3-11-3	TTCtactaaacataCAC	340_1	-16.07	41728
  341	TACCAATAGTTACCTT	2-10-4	TAccaatagttaCCTT	341_1	-20.03	42167
  342	CTTACCAATAGTTACCT	3-11-3	CTTaccaatagttaCCT	342_1	-22.29	42168
  343	TTACCAATAGTTACCT	3-10-3	TTAccaatagttaCCT	343_1	-20.03	42168
  344	CTTACCAATAGTTACC	4-10-2	CTTAccaatagttaCC	344_1	-20.03	42169
  345	TCTTACCAATAGTTACC	4-11-2	TCTTaccaatagttaCC	345_1	-21.30	42169
  346	TCAAAGCACACCACCAC	2-12-3	TCaaagcacaccacCAC	346_1	-21.69	42287
  347	ATTCAAAGCACACCACC	2-12-3	ATtcaaagcacaccACC	347_1	-21.00	42289
  348	AGACTAATCCTCTTAA	3-10-3	AGActaatcctctTAA	348_1	-17.72	43452
  349	TAGACTAATCCTCTTA	4-10-2	TAGActaatcctctTA	349_1	-19.20	43453
  350	CCCATTTCTAACATTTAC	3-12-3	CCCatttctaacattTAC	350_1	-22.93	43562
  351	ACCCATTTCTAACATT	4-10-2	ACCCatttctaacaTT	351_1	-20.64	43565
  352	AACCCATTTCTAACAT	4-10-2	AACCcatttctaacAT	352_1	-18.25	43566
  353	CCTCAACTTCACCAAT	2-10-4	CCtcaacttcacCAAT	353_1	-21.73	43634
  354	ACTGATTTCCTTAAAC	4-10-2	ACTGatttccttaaAC	354_1	-16.67	44180
  355	CACTGATTTCCTTAAAC	4-11-2	CACTgatttccttaaAC	355_1	-18.91	44180
  356	CCACTGATTTCCTTAAA	4-11-2	CCACtgatttccttaAA	356_1	-20.91	44181
  357	ACCACTGATTTCCTTA	2-10-4	ACcactgatttcCTTA	357_1	-20.98	44183
  358	CACCACTGATTTCCTT	3-10-3	CACcactgatttcCTT	358_1	-22.04	44184
  359	CTCTGCAATACACCAA	2-10-4	CTctgcaatacaCCAA	359_1	-20.90	44439
  360	ACTCTGCAATACACCA	3-10-3	ACTctgcaatacaCCA	360_1	-22.19	44440
  361	TACTCTGCAATACACCA	2-11-4	TActctgcaatacACCA	361_1	-22.32	44440
  361	TACTCTGCAATACACCA	1-1-1-10-1-1-2	TaCtctgcaatacAcCA	361_2	-19.29	44440
  361	TACTCTGCAATACACCA	1-3-1-8-1-1-2	TactCtgcaatacAcCA	361_3	-19.28	44440
  361	TACTCTGCAATACACCA	1-10-1-3-2	TactctgcaatAcacCA	361_4	-18.35	44440
  361	TACTCTGCAATACACCA	2-10-2-1-2	TActctgcaataCAcCA	361_5	-21.63	44440
  361	TACTCTGCAATACACCA	1-13-3	TactctgcaatacaCCA	361_6	-20.54	44440
  361	TACTCTGCAATACACCA	2-10-1-2-2	TActctgcaataCacCA	361_7	-20.06	44440
  361	TACTCTGCAATACACCA	1-1-1-12-2	TaCtctgcaatacacCA	361_8	-19.14	44440
  361	TACTCTGCAATACACCA	1-2-2-10-2	TacTCtgcaatacacCA	361_9	-20.33	44440
  361	TACTCTGCAATACACCA	1-3-1-10-2	TactCtgcaatacacCA	361_10	-19.13	44440
  362	TACTCTGCAATACACC	2-10-4	TActctgcaataCACC	362_1	-21.12	44441
  362	TACTCTGCAATACACC	1-1-1-11-2	TaCtctgcaatacaCC	362_2	-18.23	44441
  362	TACTCTGCAATACACC	1-1-1-10-3	TaCtctgcaatacACC	362_3	-18.78	44441
  362	TACTCTGCAATACACC	1-3-1-7-4	TactCtgcaataCACC	362_4	-20.87	44441
  362	TACTCTGCAATACACC	3-11-2	TACtctgcaatacaCC	362_5	-19.86	44441
  362	TACTCTGCAATACACC	2-2-1-9-2	TActCtgcaatacaCC	362_6	-19.44	44441
  362	TACTCTGCAATACACC	2-12-2	TActctgcaatacaCC	362_7	-18.47	44441
  362	TACTCTGCAATACACC	1-2-2-9-2	TacTCtgcaatacaCC	362_8	-19.42	44441
  362	TACTCTGCAATACACC	2-1-2-9-2	TAcTCtgcaatacaCC	362_9	-20.64	44441
  362	TACTCTGCAATACACC	1-3-1-9-2	TactCtgcaatacaCC	362_10	-18.22	44441
  363	TTACTCTGCAATACACC	2-11-4	TTactctgcaataCACC	363_1	-21.71	44441
  364	TTACTCTGCAATACAC	3-10-3	TTActctgcaataCAC	364_1	-17.75	44442
  365	TTTACTCTGCAATACAC	3-11-3	TTTactctgcaataCAC	365_1	-18.34	44442
  366	CTTTACTCTGCAATACA	2-11-4	CTttactctgcaaTACA	366_1	-20.23	44443
  367	TTTACTCTGCAATACA	2-10-4	TTtactctgcaaTACA	367_1	-17.56	44443
  368	GACCACACTTTCTACCA	2-13-2	GAccacactttctacCA	368_1	-21.72	44477
  369	GACCACACTTTCTACC	2-12-2	GAccacactttctaCC	369_1	-20.81	44478
  370	AAGAAACACCCTTCCA	2-10-4	AAgaaacaccctTCCA	370_1	-21.48	44776
  371	ATCTGCTACATATTCTT	4-11-2	ATCTgctacatattcTT	371_1	-19.88	45216
  372	ATCTGCTACATATTCT	4-10-2	ATCTgctacatattCT	372_1	-19.71	45217
  373	CATCTGCTACATATTCT	4-11-2	CATCtgctacatattCT	373_1	-21.32	45217
  374	CATCTGCTACATATTC	4-10-2	CATCtgctacatatTC	374_1	-18.82	45218
  375	TTCAACCCTAATCACT	4-10-2	TTCAaccctaatcaCT	375_1	-19.99	45246
  376	ATTCAACCCTAATCAC	2-10-4	ATtcaaccctaaTCAC	376_1	-18.67	45247
  377	CATTCAACCCTAATCA	3-10-3	CATtcaaccctaaTCA	377_1	-19.93	45248
  378	GCATTCAACCCTAATCA	3-12-2	GCAttcaaccctaatCA	378_1	-22.56	45248
  379	AGCATTCAACCCTAATC	4-11-2	AGCAttcaaccctaaTC	379_1	-22.98	45249
  380	GCATTCAACCCTAATC	4-10-2	GCATtcaaccctaaTC	380_1	-21.63	45249
  381	AGCATTCAACCCTAAT	4-10-2	AGCAttcaaccctaAT	381_1	-21.62	45250
  382	CAGCATTCAACCCTAAT	3-12-2	CAGcattcaaccctaAT	382_1	-21.12	45250
  383	TTAAATCCAGCATTCA	3-10-3	TTAaatccagcatTCA	383_1	-18.08	45258
  384	CTCCATATTTAAATCC	4-10-2	CTCCatatttaaatCC	384_1	-20.02	45266
  385	GCTCCATATTTAAATCC	4-11-2	GCTCcatatttaaatCC	385_1	-22.84	45266
  386	GCTCCATATTTAAATC	4-10-2	GCTCcatatttaaaTC	386_1	-18.78	45267
  387	AGCTCCATATTTAAAT	4-10-2	AGCTccatatttaaAT	387_1	-18.62	45268
  388	TAAGCTCCATATTTAA	3-10-3	TAAgctccatattTAA	388_1	-16.08	45270
  389	CCTAAGCTCCATATTTA	3-11-3	CCTaagctccatatTTA	389_1	-22.65	45271
  390	CTAAGCTCCATATTTA	4-10-2	CTAAgctccatattTA	390_1	-18.81	45271
  391	CCTAAGCTCCATATTT	4-10-2	CCTAagctccatatTT	391_1	-21.57	45272
  392	TCTACCCTAAATTCCC	2-11-3	TCtaccctaaattCCC	392_1	-23.00	45560
  393	CACATCTTGTATACAA	3-10-3	CACatcttgtataCAA	393_1	-16.65	45627
  394	ACACATCTTGTATACA	4-10-2	ACACatcttgtataCA	394_1	-17.95	45628
  395	CTACACATCTTGTATAC	3-11-3	CTAcacatcttgtaTAC	395_1	-19.13	45629
  396	TACACATCTTGTATAC	3-10-3	TACacatcttgtaTAC	396_1	-16.73	45629
  397	CTTGACTACACATCTT	3-10-3	CTTgactacacatCTT	397_1	-18.89	45635
  398	CTCTACAACAGTCCCA	3-11-2	CTCtacaacagtccCA	398_1	-22.06	45709
  399	TCTCTACAACAGTCCCA	2-13-2	TCtctacaacagtccCA	399_1	-21.70	45709
  400	ATAACATTACTCTTAACA	3-12-3	ATAacattactcttaACA	400_1	-17.03	46215
  401	TTTGACATTCCATCTCC	2-12-3	TTtgacattccatcTCC	401_1	-21.62	46256
  402	CTTTGACATTCCATCTC	2-11-4	CTttgacattccaTCTC	402_1	-21.88	46257
  403	TCTTTGACATTCCATCTC	4-12-2	TCTTtgacattccatcTC	403_1	-22.41	46257
  404	TTTGACATTCCATCTC	3-10-3	TTTgacattccatCTC	404_1	-19.40	46257
  405	ATCTTTGACATTCCATC	2-11-4	ATctttgacattcCATC	405_1	-20.53	46259
  406	TATCTTTGACATTCCAT	2-11-4	TAtctttgacattCCAT	406_1	-21.32	46260
  407	TACTATCTTTGACATTC	4-11-2	TACTatctttgacatTC	407_1	-18.39	46263
  408	TACTATCTTTGACATT	4-10-2	TACTatctttgacaTT	408_1	-16.84	46264
  409	CTGTATACACCATCCC	2-12-2	CTgtatacaccatcCC	409_1	-21.84	46392
  410	TCTGTATACACCATCC	4-10-2	TCTGtatacaccatCC	410_1	-22.73	46393
  411	TTTCTGACTCCCTATCC	2-13-2	TTtctgactccctatCC	411_1	-22.48	46420
  412	CCTATGTTAATACTTTC	4-11-2	CCTAtgttaatacttTC	412_1	-19.53	46505
  413	CTATGTTAATACTTTC	4-10-2	CTATgttaatacttTC	413_1	-16.09	46505
  414	CCTATGTTAATACTTT	4-10-2	CCTAtgttaatactTT	414_1	-17.85	46506
  415	TCCTATGTTAATACTT	3-10-3	TCCtatgttaataCTT	415_1	-18.47	46507
  416	ATCCTATGTTAATACT	4-10-2	ATCCtatgttaataCT	416_1	-18.71	46508
  417	ATTTCATTAAGTCACCC	3-11-3	ATTtcattaagtcaCCC	417_1	-22.16	47364
  418	ATTTCATTAAGTCACC	2-10-4	ATttcattaagtCACC	418_1	-18.79	47365
  419	CTCTCCTCAAGATCAAC	3-11-3	CTCtcctcaagatcAAC	419_1	-20.29	48110
  420	CTCTCCTCAAGATCAA	3-10-3	CTCtcctcaagatCAA	420_1	-20.33	48111
  421	CCATACAGTATATACA	4-10-2	CCATacagtatataCA	421_1	-19.53	48186
  422	CAACTATTATCTTCTT	2-10-4	CAactattatctTCTT	422_1	-16.38	48221
  423	ACAACTATTATCTTCT	3-10-3	ACAactattatctTCT	423_1	-16.60	48222
  424	TTGCTTCCAATTTATTT	4-11-2	TTGCttccaatttatTT	424_1	-19.93	50282
  425	ATCTCATGACCACCTAA	3-11-3	ATCtcatgaccaccTAA	425_1	-21.74	51241
  425	ATCTCATGACCACCTAA	1-1-1-9-2-1-2	AtCtcatgaccaCCTAA	425_2	-21.11	51241
  425	ATCTCATGACCACCTAA	1-1-1-8-1-2-3	AtCtcatgaccAccTAA	425_3	-19.96	51241
  425	ATCTCATGACCACCTAA	1-12-4	AtctcatgaccacCTAA	425_4	-20.40	51241
  425	ATCTCATGACCACCTAA	3-10-1-1-2	ATCtcatgaccacCTAA	425_5	-20.66	51241
  425	ATCTCATGACCACCTAA	1-1-1-10-1-1-2	AtCtcatgaccacCTAA	425_6	-18.72	51241
  425	ATCTCATGACCACCTAA	1-1-1-9-1-1-3	AtCtcatgaccaCcTAA	425_7	-20.59	51241
  425	ATCTCATGACCACCTAA	1-2-2-7-1-1-3	AtcTCatgaccaCcTAA	425_8	-21.48	51241
  425	ATCTCATGACCACCTAA	1-3-1-8-4	AtctCatgaccacCTAA	425_9	-21.07	51241
  425	ATCTCATGACCACCTAA	1-1-3-8-1-1-2	AtCTCatgaccacCtAA	425_10	-21.27	51241
  426	TCTCATGACCACCTAA	2-10-4	TCtcatgaccacCTAA	426_1	-21.25	51241
  427	ATCTCATGACCACCTA	3-10-3	ATCtcatgaccacCTA	427_1	-22.56	51242
  428	TATCTCATGACCACCTA	2-12-3	TAtctcatgaccacCTA	428_1	-21.88	51242
  429	TTTATCTCATGACCACC	2-11-4	TTtatctcatgacCACC	429_1	-22.37	51244
  430	TTTATCTCATGACCAC	2-10-4	TTtatctcatgaCCAC	430_1	-19.56	51245
  431	ATTCTTACCGTCTTTA	4-10-2	ATTCttaccgtcttTA	431_1	-19.52	51358
  432	TATTCTTACCGTCTTTA	3-11-3	TATtcttaccgtctTTA	432_1	-20.10	51358
  433	TATTCTTACCGTCTTT	2-10-4	TAttcttaccgtCTTT	433_1	-19.30	51359
  434	TTATTCTTACCGTCTTT	2-11-4	TTattcttaccgtCTTT	434_1	-19.99	51359
  435	ATCTGATCTCACACAT	3-10-3	ATCtgatctcacaCAT	435_1	-19.62	51438
  436	CATCTGATCTCACACAT	4-11-2	CATCtgatctcacacAT	436_1	-20.82	51438
  437	ACTTCCAGATTTCTACA	2-11-4	ACttccagatttcTACA	437_1	-21.44	51953
  438	TTTATGTTTACTTCAT	3-10-3	TTTatgtttacttCAT	438_1	-16.05	52150
  439	TAAAGATCCCATCACTC	3-11-3	TAAagatcccatcaCTC	439_1	-20.31	52549
  440	TAAAGATCCCATCACT	4-10-2	TAAAgatcccatcaCT	440_1	-18.82	52550
  441	CCTAAAGATCCCATCAC	2-12-3	CCtaaagatcccatCAC	441_1	-22.32	52551
  442	ATCATCAGTTACATCA	4-10-2	ATCAtcagttacatCA	442_1	-18.64	52579
  443	ACTCTCACTGTAACTTT	4-11-2	ACTCtcactgtaactTT	443_1	-19.76	53012
  444	AACTCTCACTGTAACTT	3-11-3	AACtctcactgtaaCTT	444_1	-18.53	53013
  445	ACTCTCACTGTAACTT	3-10-3	ACTctcactgtaaCTT	445_1	-19.04	53013
  446	AACTCTCACTGTAACT	4-10-2	AACTctcactgtaaCT	446_1	-17.97	53014
  447	CAACTCTCACTGTAACT	4-11-2	CAACtctcactgtaaCT	447_1	-20.01	53014
  448	CCTTTCATTAACATTTA	3-11-3	CCTttcattaacatTTA	448_1	-19.03	54198
  449	TTCCTTTCATTAACATTT	4-12-2	TTCCtttcattaacatTT	449_1	-19.92	54199
  450	TAATCCTATTCCAACT	3-10-3	TAAtcctattccaACT	450_1	-18.05	54232
  451	CTAATCCTATTCCAAC	2-10-4	CTaatcctattcCAAC	451_1	-18.65	54233
  452	CTCTAATCCTATTCCA	3-10-3	CTCtaatcctattCCA	452_1	-22.58	54235
  453	TCTCTAATCCTATTCC	4-10-2	TCTCtaatcctattCC	453_1	-21.78	54236
  454	TTGTCTCTAATCCTATT	2-11-4	TTgtctctaatccTATT	454_1	-19.70	54238
  455	TTGTCTCTAATCCTAT	2-10-4	TTgtctctaatcCTAT	455_1	-19.45	54239
  456	TCTTTAAGCTTCCCAC	2-10-4	TCtttaagcttcCCAC	456_1	-22.96	54609
  457	AAACTACCCTGCACAA	3-10-3	AAActaccctgcaCAA	457_1	-18.41	54924
  458	CCATGCTACATAAACC	4-10-2	CCATgctacataaaCC	458_1	-22.25	55337
  459	TCCATGCTACATAAAC	4-10-2	TCCAtgctacataaAC	459_1	-18.64	55338
  460	ACTCCTAAGAATTACA	4-10-2	ACTCctaagaattaCA	460_1	-17.62	59565
  461	GAAACTATTACTCCTA	2-10-4	GAaactattactCCTA	461_1	-19.06	59574
  462	TGAAACTATTACTCCT	3-10-3	TGAaactattactCCT	462_1	-19.30	59575
  463	ATGAAACTATTACTCC	2-10-4	ATgaaactattaCTCC	463_1	-17.96	59576
  464	AACAACTCATGCCACA	2-10-4	AAcaactcatgcCACA	464_1	-19.72	60012
  465	AAATATTGCCACCATT	2-10-4	AAatattgccacCATT	465_1	-17.78	60298
  466	GTTACATATTCTTTCAC	3-11-3	GTTacatattctttCAC	466_1	-18.76	60448
  467	TCATACTTGCTTTAAT	4-10-2	TCATacttgctttaAT	467_1	-17.29	60821
  468	ATCCTGATAATTAACT	4-10-2	ATCCtgataattaaCT	468_1	-17.73	61925
  469	CCTTAATCTGTATCAC	3-10-3	CCTtaatctgtatCAC	469_1	-19.92	62287
  470	ATACACAGCACATATT	2-10-4	ATacacagcacaTATT	470_1	-17.58	62422
  471	TCAGAATAATTCTCCT	3-10-3	TCAgaataattctCCT	471_1	-19.81	62443
  472	TCTTCAGCTTTCTAAAT	4-11-2	TCTTcagctttctaaAT	472_1	-18.58	64113
  473	AGTCCTTCCTTTAACCA	2-13-2	AGtccttcctttaacCA	473_1	-22.20	64461
  474	TAGTCCTTCCTTTAACC	2-13-2	TAgtccttcctttaaCC	474_1	-22.12	64462
  475	TTTAACCTTGCTTATA	2-10-4	TTtaaccttgctTATA	475_1	-17.50	65272
  476	ATCCCTTTGTAATCAT	4-10-2	ATCCctttgtaatcAT	476_1	-20.31	66840
  477	CTTGCATTTCTAATTAC	3-11-3	CTTgcatttctaatTAC	477_1	-18.09	67426
  478	CTTGTCAAATCATTTCT	4-11-2	CTTGtcaaatcatttCT	478_1	-19.10	68194
  479	CCATCTAATGATTATT	4-10-2	CCATctaatgattaTT	479_1	-17.28	68328
  480	TATCAGTTATCCAATA	4-10-2	TATCagttatccaaTA	480_1	-17.39	68805
  481	TCACTGCCATCAATAC	4-10-2	TCACtgccatcaatAC	481_1	-19.71	68921
  482	TGTCATCTACAAATCA	4-10-2	TGTCatctacaaatCA	482_1	-18.01	70133
  483	CTCTTTAGATTCATCC	4-10-2	CTCTttagattcatCC	483_1	-20.94	72377
  484	ACTCTTTAGATTCATC	2-10-4	ACtctttagattCATC	484_1	-17.81	72378
  485	CAACTCTATGACTACC	2-10-4	CAactctatgacTACC	485_1	-20.07	72826
  486	ACCTGTAATACTTCTT	4-10-2	ACCTgtaatacttcTT	486_1	-19.67	72861
  487	GAATTCTTTATTCCTCC	2-11-4	GAattctttattcCTCC	487_1	-22.53	72887
  488	ATCTGAATCAAACCTT	2-10-4	ATctgaatcaaaCCTT	488_1	-17.97	73474
  489	ACTTTACTGCCATAATC	3-11-3	ACTttactgccataATC	489_1	-19.60	73992
  490	TTACTCTTAGCAACCT	4-10-2	TTACtcttagcaacCT	490_1	-20.19	74791
  491	CACCAGTATTTCTTCTT	4-11-2	CACCagtatttcttcTT	491_1	-22.15	74851
  492	TTCACCAGTATTTCTTC	4-11-2	TTCAccagtatttctTC	492_1	-20.43	74853
  493	CCAAATAAGCAAACTC	3-10-3	CCAaataagcaaaCTC	493_1	-17.54	75840
  494	CCCAAATAAGCAAACT	4-10-2	CCCAaataagcaaaCT	494_1	-20.23	75841
  495	GACTACATTCTCAATA	3-10-3	GACtacattctcaATA	495_1	-17.49	76238
  496	TTGTCAATCTTTATTCT	4-11-2	TTGTcaatctttattCT	496_1	-18.85	76254
  497	AGCTTACCAAATATTC	4-10-2	AGCTtaccaaatatTC	497_1	-18.68	76811
  498	TTACACATGTATATCC	3-10-3	TTAcacatgtataTCC	498_1	-18.23	77114
  499	ATCCTGTTAATACCAT	2-10-4	ATcctgttaataCCAT	499_1	-20.41	80468
  500	TTCTTAGTCACACACA	4-10-2	TTCTtagtcacacaCA	500_1	-19.37	81047
  501	TTCTGTTTCCATTTACA	4-11-2	TTCTgtttccatttaCA	501_1	-21.31	82233
  502	TCTATATCAAGTTCCTT	2-11-4	TCtatatcaagttCCTT	502_1	-20.95	84166
  503	ATTCAGTTACCAACTA	3-10-3	ATTcagttaccaaCTA	503_1	-18.37	85392
  504	GCTTCTACTTAAATAT	3-10-3	GCTtctacttaaaTAT	504_1	-17.58	86974
  505	CCCTCAAAGTAATTTC	4-10-2	CCCTcaaagtaattTC	505_1	-20.53	87728
  506	AACATGTAATTTCCAT	2-10-4	AAcatgtaatttCCAT	506_1	-17.21	87810
  507	CCAGACTCCAATATTT	4-10-2	CCAGactccaatatTT	507_1	-20.78	88417
  508	CTTAGACTTCACCTTTC	2-11-4	CTtagacttcaccTTTC	508_1	-20.56	88991
  509	CTGCTTAATTATATCA	4-10-2	CTGCttaattatatCA	509_1	-18.85	90228
  510	AAATTGTCTACCTTCCT	2-12-3	AAattgtctaccttCCT	510_1	-20.62	90474
  511	CACTTAGAATATCCCT	2-10-4	CActtagaatatCCCT	511_1	-22.28	91625
  512	ATCCAAAGTTTCTTTC	4-10-2	ATCCaaagtttcttTC	512_1	-18.64	91885
  513	ATATTTGTCACCTAAC	4-10-2	ATATttgtcacctaAC	513_1	-17.12	92976
  514	CTATTCTCAGTATTAT	3-10-3	CTAttctcagtatTAT	514_1	-17.42	94304
  515	CCATTCAATGATCACT	2-10-4	CCattcaatgatCACT	515_1	-20.55	94528
  516	CACTAGTACTCTTATT	4-10-2	CACTagtactcttaTT	516_1	-18.01	95653
  517	GCCACAACATCTATTT	4-10-2	GCCAcaacatctatTT	517_1	-21.53	96751
  518	AGCACATATACCATCA	4-10-2	AGCAcatataccatCA	518_1	-21.98	97636
  519	GTCATCTAACTTCTTAC	3-11-3	GTCatctaacttctTAC	519_1	-19.25	98480
  520	TGTCATCTAACTTCTTA	4-11-2	TGTCatctaacttctTA	520_1	-19.69	98481
  521	CCCTTATAGTTATTAA	3-10-3	CCCttatagttatTAA	521_1	-19.32	99646
  522	TCCATAGAATTCTTCA	4-10-2	TCCAtagaattcttCA	522_1	-19.92	100334
  523	TTGATTCCACCATTAA	3-10-3	TTGattccaccatTAA	523_1	-18.05	101110
  524	CAGCCATAAACTATAT	4-10-2	CAGCcataaactatAT	524_1	-18.60	101898
  525	TATGACTTATTCCATA	2-10-4	TAtgacttattcCATA	525_1	-17.88	102558
  526	GTTAACCTATATTTCA	4-10-2	GTTAacctatatttCA	526_1	-17.69	103589
  527	TGTCTATTCTCTTCATT	4-11-2	TGTCtattctcttcaTT	527_1	-20.62	104309
  528	TTACTCTTTGATTTCAT	3-11-3	TTActctttgatttCAT	528_1	-18.39	105686
  529	GATAATTCCAAATCCC	2-10-4	GAtaattccaaaTCCC	529_1	-20.99	107972
  530	TCTTATCCTTGAATTTC	4-11-2	TCTTatccttgaattTC	530_1	-18.85	108257
  531	ATATCCCTTGATTATCC	3-11-3	ATAtcccttgattaTCC	531_1	-22.75	109407
  532	TTAGTATACCCTTTAT	3-10-3	TTAgtatacccttTAT	532_1	-18.67	110210
  533	CTCTTTGTCAAATACT	4-10-2	CTCTttgtcaaataCT	533_1	-18.16	110768
  534	CCAAACTGTCTTCTAAT	2-11-4	CCaaactgtcttcTAAT	534_1	-19.87	111811
  535	TCCAAACTGTCTTCTAA	3-12-2	TCCaaactgtcttctAA	535_1	-18.33	111812
  536	CCAGCATATTATATAC	3-10-3	CCAgcatattataTAC	536_1	-18.96	112149
  537	TCCAGCATATTATATA	4-10-2	TCCAgcatattataTA	537_1	-19.41	112150
  538	TCATTGAACAACTCTTC	4-11-2	TCATtgaacaactctTC	538_1	-18.01	112945
  539	CTGCCATCTTTATTTAT	4-11-2	CTGCcatctttatttAT	539_1	-21.89	113533
  540	TGAAACATTCTTCCCAC	2-12-3	TGaaacattcttccCAC	540_1	-19.76	114274
  541	TTTATTAGATTACTCC	2-10-4	TTtattagattaCTCC	541_1	-17.38	114495
  542	TTCCAGCTTATTTACCT	3-12-2	TTCcagcttatttacCT	542_1	-21.28	114831
  543	AGCATCATATAAACCT	3-10-3	AGCatcatataaaCCT	543_1	-20.62	115355
  544	GTACTTACACATCTAT	2-10-4	GTacttacacatCTAT	544_1	-18.96	116105
  545	TGTACTTACACATCTA	3-10-3	TGTacttacacatCTA	545_1	-19.38	116106
  546	ATTTCTCTATGTCACAT	3-11-3	ATTtctctatgtcaCAT	546_1	-19.28	117096
  547	CAAACCTACGTCTCTC	2-10-4	CAaacctacgtcTCTC	547_1	-20.87	117189
  548	GTATTTACTCTTTACCT	3-11-3	GTAtttactctttaCCT	548_1	-22.15	117476
  549	CTAATGCAATAACCCA	2-10-4	CTaatgcaataaCCCA	549_1	-21.79	118293
  550	ACTAATGCAATAACCC	3-10-3	ACTaatgcaataaCCC	550_1	-20.53	118294
  551	AGCTCTAAACCTTCAA	3-10-3	AGCtctaaaccttCAA	551_1	-20.51	118756
  552	TATTTGTCACCAAACC	3-10-3	TATttgtcaccaaACC	552_1	-19.63	119621
  553	CTCAGACATCTCAATA	4-10-2	CTCAgacatctcaaTA	553_1	-19.25	120655
  554	TCTCAGCTTCTTCAAAT	2-12-3	TCtcagcttcttcaAAT	554_1	-18.33	123733
  555	GCCAATACCCACAAAC	3-10-3	GCCaatacccacaAAC	555_1	-22.03	124163
  556	CCTCTGACAACCATTA	4-10-2	CCTCtgacaaccatTA	556_1	-22.57	125512
  557	CAGATAACTCTAAACC	4-10-2	CAGAtaactctaaaCC	557_1	-18.43	126882
  558	CTAACTGTTTCTCAATT	3-11-3	CTAactgtttctcaATT	558_1	-18.10	127105
  559	CCAAGATAATCATCAT	3-10-3	CCAagataatcatCAT	559_1	-18.37	127809
  560	TACATATTGTACTTCT	4-10-2	TACAtattgtacttCT	560_1	-17.48	129020
  561	TAGCCTACTTTAATAT	4-10-2	TAGCctactttaatAT	561_1	-18.67	129205
  562	CATTTACAAGCACATA	2-10-4	CAtttacaagcaCATA	562_1	-17.81	129928
  563	TTATTCTGACACACTT	3-10-3	TTAttctgacacaCTT	563_1	-17.49	130020
  564	TACATTGACACCTAAT	4-10-2	TACAttgacacctaAT	564_1	-17.37	130884
  565	TTTACATTGACACCTA	2-10-4	TTtacattgacaCCTA	565_1	-19.42	130886
  566	TGTATATAACTATTCC	4-10-2	TGTAtataactattCC	566_1	-17.79	131404
  567	GAATCTTCTAATTCCAC	2-11-4	GAatcttctaattCCAC	567_1	-20.40	132514
  568	TGCTCACTAACTACAC	3-10-3	TGCtcactaactaCAC	568_1	-20.66	133367
  569	TGCTACCATCATTACCT	2-13-2	TGctaccatcattacCT	569_1	-21.32	136198
  570	TTTATCAATATCTTCTCACT	1-13-1-1-1-1-2	TttatcaatatcttCtCaCT	570_1	-19.69	5784
  570	TTTATCAATATCTTCTCACT	1-2-1-10-1-2-3	TttAtcaatatcttCtcACT	570_2	-19.67	5784
  570	TTTATCAATATCTTCTCACT	1-5-1-7-1-2-3	TttatcAatatcttCtcACT	570_3	-19.65	5784
  570	TTTATCAATATCTTCTCACT	1-1-1-11-1-3-2	TtTatcaatatcttCtcaCT	570_4	-19.75	5784
  570	TTTATCAATATCTTCTCACT	1-2-1-2-1-11-2	TttAtcAatatcttctcaCT	570_5	-18.21	5784
  570	TTTATCAATATCTTCTCACT	1-4-1-8-1-3-2	TttatCaatatcttCtcaCT	570_6	-19.69	5784
  570	TTTATCAATATCTTCTCACT	1-2-1-2-1-9-1-1-2	TttAtcAatatcttctCaCT	570_7	-18.88	5784
  570	TTTATCAATATCTTCTCACT	1-2-1-1-1-11-3	TttAtCaatatcttctcACT	570_8	-19.36	5784
  570	TTTATCAATATCTTCTCACT	1-4-1-10-1-1-2	TttatCaatatcttctCaCT	570_9	-19.38	5784
  570	TTTATCAATATCTTCTCACT	2-1-1-10-1-1-1-1-2	TTTAtcaatatcttCtCaCT	570_10	-20.60	5784
  570	TTTATCAATATCTTCTCACT	1-4-1-8-1-1-1-1-2	TttatCaatatcttCtCaCT	570_11	-20.36	5784
  570	TTTATCAATATCTTCTCACT	1-2-1-1-1-8-1-2-3	TttAtCaatatcttCtcACT	570_12	-20.34	5784
  570	TTTATCAATATCTTCTCACT	1-2-1-2-1-7-1-3-2	TttAtcAatatcttCtcaCT	570_13	-19.19	5784
  570	TTTATCAATATCTTCTCACT	1-1-2-1-1-10-1-1-2	TtTAtCaatatcttctCaCT	570_14	-21.24	5784
  571	TTTATCAATATCTTCTCAC	1-12-2-1-3	TttatcaatatctTCtCAC	571_1	-19.16	5785
  571	TTTATCAATATCTTCTCAC	2-1-1-1-1-6-2-2-3	TTrAtCaatatcTTctCAC	571_2	-20.17	5785
  571	TTTATCAATATCTTCTCAC	3-2-1-7-2-2-2	TTTatCaatatctTCtcAC	571_3	-19.79	5785
  571	TTTATCAATATCTTCTCAC	1-2-3-8-1-2-2	TttATCaatatcttCtcAC	571_4	-18.78	5785
  571	TTTATCAATATCTTCTCAC	1-4-1-9-4	TttatCaatatcttcTCAC	571_5	-19.06	5785
  571	TTTATCAATATCTTCTCAC	2-1-1-1-1-8-1-1-3	TTrAtCaatatcttCtCAC	571_6	-19.75	5785
  571	TTTATCAATATCTTCTCAC	1-1-1-2-1-6-1-3-3	TtTatCaatatcTtctCAC	571_7	-19.11	5785
  571	TTTATCAATATCTTCTCAC	2-1-3-6-1-4-2	TTTATCaatatcTtctcAC	571_8	-19.13	5785
  571	TTTATCAATATCTTCTCAC	4-12-3	TTTAtcaatatcttctCAC	571_9	-20.38	5785
  571	TTTATCAATATCTTCTCAC	1-1-2-1-1-6-1-3-3	TtTAtCaatatoTtctCAC	571_10	-20.24	5785
  571	TTTATCAATATCTTCTCAC	2-1-1-1-1-7-2-2-2	TTrAtCaatatctTCtcAC	571_11	-18.65	5785
  571	TTTATCAATATCTTCTCAC	3-2-1-8-1-1-3	TTTatCaatatottCtCAC	571_12	-20.89	5785
  571	TTTATCAATATCTTCTCAC	1-3-2-8-1-1-3	TttaTCaatatottCtCAC	571_13	-19.96	5785
  571	TTTATCAATATCTTCTCAC	1-2-1-1-1-9-4	TttAtCaatatottcTCAC	571_14	-19.16	5785
  572	TTTATCAATATCTTCTCA	2-1-1-1-1-7-2-1-2	TTrAtCaatatctTCtCA	572_1	-18.69	5786
  572	TTTATCAATATCTTCTCA	3-2-1-6-1-1-1-1-2	TTTatCaatatoTtCtCA	572_2	-19.36	5786
  572	TTTATCAATATCTTCTCA	1-4-1-6-1-1-4	TttatCaatatoTtCTCA	572_3	-19.19	5786
  572	TTTATCAATATCTTCTCA	1-2-3-6-1-2-3	TttATCaatatoTtcTCA	572_4	-19.56	5786
  572	TTTATCAATATCTTCTCA	4-1-1-7-1-2-2	TTTAtCaatatotTctCA	572_5	-19.37	5786
  572	TTTATCAATATCTTCTCA	1-2-3-8-1-1-2	TttATCaatatottCtCA	572_6	-18.83	5786
  572	TTTATCAATATCTTCTCA	3-2-1-9-3	TTTatCaatatottcTCA	572_7	-19.07	5786
  572	TTTATCAATATCTTCTCA	1-2-1-10-4	TttAtcaatatottCTCA	572_8	-18.10	5786
  572	TTTATCAATATCTTCTCA	4-10-1-1-2	TTTAtcaatatottCtCA	572_9	-19.31	5786
  572	TTTATCAATATCTTCTCA	2-1-3-6-1-1-1-1-2	TTTATCaatatoTtCtCA	572_10	-20.15	5786
  572	TTTATCAATATCTTCTCA	3-2-1-6-1-2-3	TTTatCaatatoTtcTCA	572_11	-19.59	5786
  572	TTTATCAATATCTTCTCA	1-1-2-1-1-7-2-1-2	TtTAtCaatatotTCtCA	572_12	-19.64	5786
  572	TTTATCAATATCTTCTCA	4-9-1-1-3	TTTAtcaatatotTcTCA	572_13	-19.90	5786
  572	TTTATCAATATCTTCTCA	1-3-2-8-4	TttaTCaatatcttCTCA	572_14	-19.80	5786
  573	TATACCTTTCTTTAACCCTT	1-4-1-10-1-1-2	TatacCtttctttaacCcTT	573_1	-22.72	8116
  573	TATACCTTTCTTTAACCCTT	2-4-1-11-2	TAtaccTttctttaacccTT	573_2	-22.80	8116
  573	TATACCTTTCTTTAACCCTT	1-3-1-10-1-2-2	TataCctttctttaaCccTT	573_3	-22.72	8116
  573	TATACCTTTCTTTAACCCTT	1-4-1-9-1-2-2	TatacCtttctttaaCccTT	573_4	-22.82	8116
  573	TATACCTTTCTTTAACCCTT	1-5-1-9-1-1-2	TataccTttctttaacCcTT	573_5	-22.35	8116
  573	TATACCTTTCTTTAACCCTT	1-5-1-1-1-2	TatacctttctttaacCcTT	573_6	-21.83	8116
  573	TATACCTTTCTTTAACCCTT	1-2-1-1-1-10-1-1-2	TatAcCtttctttaacCcTT	573_7	-22.91	8116
  573	TATACCTTTCTTTAACCCTT	2-2-1-1-1-11-2	TAtaCcTttctttaacccTT	573_8	-23.58	8116
  573	TATACCTTTCTTTAACCCTT	2-3-1-12-2	TAtacCtttctttaacccTT	573_9	-23.17	8116
  573	TATACCTTTCTTTAACCCTT	1-3-1-8-2-1-1-1-2	TataCctttctttAAcCcTT	573_10	-23.35	8116
  573	TATACCTTTCTTTAACCCTT	2-2-1-1-1-7-1-1-1-1-2	TAtaCcTttctttaAcCcTT	573_11	-24.68	8116
  573	TATACCTTTCTTTAACCCTT	2-4-1-8-2-1-2	TAtaccTttctttaaCCcTT	573_12	-25.86	8116
  573	TATACCTTTCTTTAACCCTT	2-3-1-9-1-2-2	TAtacCtttctttaaCccTT	573_13	-23.96	8116
  573	TATACCTTTCTTTAACCCTT	2-3-1-10-1-1-2	TAtacCtttctttaacCcTT	573_14	-23.85	8116
  574	TTATACCTTTCTTTAACCCT	1-1-1-10-1-4-2	TtAtacctttcttTaaccCT	574_1	-22.31	8117
  574	TTATACCTTTCTTTAACCCT	1-13-1-1-1-1-2	TtatacctttctttAaCcCT	574_2	-22.38	8117
  574	TTATACCTTTCTTTAACCCT	1-1-1-3-1-11-2	TtAtacCtttctttaaccCT	574_3	-22.47	8117
  574	TTATACCTTTCTTTAACCCT	1-3-1-1-1-7-1-3-2	TtatAcCtttctttAaccCT	574_4	-22.68	8117
  574	TTATACCTTTCTTTAACCCT	1-4-1-8-1-3-2	TtataCctttctttAaccCT	574_5	-22.38	8117
  574	TTATACCTTTCTTTAACCCT	1-1-1-13-1-1-2	TtAtacctttctttaaCcCT	574_6	-22.36	8117
  574	TTATACCTTTCTTTAACCCT	1-3-1-11-1-1-2	TtatAcctttctttaaCcCT	574_7	-22.46	8117
  574	TTATACCTTTCTTTAACCCT	1-1-1-2-1-12-2	TtAtaCctttctttaaccCT	574_8	-22.36	8117
  574	TTATACCTTTCTTTAACCCT	1-5-1-11-2	TtatacCtttctttaaccCT	574_9	-22.37	8117
  574	TTATACCTTTCTTTAACCCT	1-1-1-2-1-10-1-1-2	TtAtaCctttctttaaCcCT	574_10	-23.14	8117
  574	TTATACCTTTCTTTAACCCT	1-1-1-3-1-9-1-1-2	TtAtacCtttctttaaCcCT	574_11	-23.25	8117
  574	TTATACCTTTCTTTAACCCT	1-1-1-3-1-10-3	TtAtacCtttctttaacCCT	574_12	-24.75	8117
  574	TTATACCTTTCTTTAACCCT	1-1-1-2-2-11-2	TtAtaCCtttctttaaccCT	574_13	-24.85	8117
  574	TTATACCTTTCTTTAACCCT	1-3-1-1-1-11-2	TtatAcCtttctttaaccCT	574_14	-22.56	8117
  575	TTTATACCTTTCTTTAACCC	1-2-1-9-1-4-2	TttAtacctttctTtaacCC	575_1	-21.69	8118
  575	TTTATACCTTTCTTTAACCC	1-12-1-4-2	TttatacctttctTtaacCC	575_2	-21.59	8118
  575	TTTATACCTTTCTTTAACCC	1-12-1-1-1-2-2	TttatacctttctTtAacCC	575_3	-21.71	8118
  575	TTTATACCTTTCTTTAACCC	1-4-1-10-1-1-2	TttatAcctttctttaAcCC	575_4	-21.90	8118
  575	TTTATACCTTTCTTTAACCC	1-13-1-3-2	TttatacctttcttTaacCC	575_5	-22.01	8118
  575	TTTATACCTTTCTTTAACCC	2-1-1-14-2	TTTAtacctttctttaacCC	575_6	-22.20	8118
  575	TTTATACCTTTCTTTAACCC	1-14-2-1-2	TttatacctttctttAAcCC	575_7	-22.02	8118
  575	TTTATACCTTTCTTTAACCC	1-14-1-2-2	TttatacctttctttAacCC	575_8	-21.41	8118
  575	TTTATACCTTTCTTTAACCC	1-15-1-1-2	TttatacctttctttaAcCC	575_9	-21.71	8118
  575	TTTATACCTTTCTTTAACCC	2-1-1-9-1-4-2	TTTAtacctttctTtaacCC	575_10	-22.50	8118
  575	TTTATACCTTTCTTTAACCC	1-2-1-10-1-3-2	TttAtacctttcttTaacCC	575_11	-22.11	8118
  575	TTTATACCTTTCTTTAACCC	1-4-2-8-2-1-2	TttatACctttctttAAcCC	575_12	-23.40	8118
  575	TTTATACCTTTCTTTAACCC	1-2-1-2-1-9-1-1-2	TttAtaCctttctttaAcCC	575_13	-22.59	8118
  575	TTTATACCTTTCTTTAACCC	1-1-2-14-2	TtTAtacctttctttaacCC	575_14	-23.15	8118
  576	TTTTATACCTTTCTTTAACC	1-1-1-10-2-3-2	TtTtatacctttcTTtaaCC	576_1	-21.12	8119
  576	TTTTATACCTTTCTTTAACC	1-3-1-8-1-4-2	TtttAtacctttcTttaaCC	576_2	-20.10	8119
  576	TTTTATACCTTTCTTTAACC	1-1-1-10-1-2-4	TtTtatacctttcTttAACC	576_3	-21.45	8119
  576	TTTTATACCTTTCTTTAACC	3-11-1-1-1-1-2	TTTtatacctttctTtAaCC	576_4	-21.54	8119
  576	TTTTATACCTTTCTTTAACC	2-4-1-7-1-3-2	TTttatAcctttctTtaaCC	576_5	-20.80	8119
  576	TTTTATACCTTTCTTTAACC	1-14-1-2-2	TtttatacctttcttTaaCC	576_6	-20.22	8119
  576	TTTTATACCTTTCTTTAACC	1-15-1-1-2	TtttatacctttctttAaCC	576_7	-19.61	8119
  576	TTTTATACCTTTCTTTAACC	1-5-1-10-3	TtttatAcctttctttaACC	576_8	-20.51	8119
  576	TTTTATACCTTTCTTTAACC	1-1-2-14-2	TtTTatacctttctttaaCC	576_9	-21.03	8119
  576	TTTTATACCTTTCTTTAACC	1-1-2-10-1-1-1-1-2	TtTTatacctttctTtAaCC	576_10	-21.46	8119
  576	TTTTATACCTTTCTTTAACC	2-2-1-9-1-3-2	TTttAtacctttctTtaaCC	576_11	-20.70	8119
  576	TTTTATACCTTTCTTTAACC	1-5-1-7-1-3-2	TtttatAcctttctTtaaCC	576_12	-19.99	8119
  576	TTTTATACCTTTCTTTAACC	1-1-1-12-2-1-2	TtTtatacctttcttTAaCC	576_13	-21.68	8119
  576	TTTTATACCTTTCTTTAACC	1-1-1-1-1-13-2	TtTtAtacctttctttaaCC	576_14	-19.89	8119
  577	TTTTTATACCTTTCTTTAAC	1-12-1-2-4	TttttatacctttCttTAAC	577_1	-19.19	8120
  577	TTTTTATACCTTTCTTTAAC	1-2-1-9-1-1-2-1-2	TttTtatacctttCtTTaAC	577_2	-18.96	8120
  577	TTTTTATACCTTTCTTTAAC	2-12-3-1-2	TTtttatacctttcTTTaAC	577_3	-19.52	8120
  577	TTTTTATACCTTTCTTTAAC	1-1-1-2-1-7-2-3-2	TtTttAtacctttCTttaAC	577_4	-18.71	8120
  577	TTTTTATACCTTTCTTTAAC	4-9-1-1-1-2-2	TTTTtatacctttCtTtaAC	577_5	-19.85	8120
  577	TTTTTATACCTTTCTTTAAC	3-1-1-8-1-1-1-1-3	TTTtTatacctttCtTtAAC	577_6	-20.08	8120
  577	TTTTTATACCTTTCTTTAAC	2-1-2-8-2-2-3	TTtTTatacctttCTttAAC	577_7	-20.97	8120
  577	TTTTTATACCTTTCTTTAAC	1-1-2-10-2-1-3	TtTTtatacctttcTTTAAC	577_8	-18.89	8120
  577	TTTTTATACCTTTCTTTAAC	1-3-2-7-1-4-2	TtttTAtacctttCtttaAC	577_9	-18.97	8120
  577	TTTTTATACCTTTCTTTAAC	1-2-1-9-2-1-1-1-2	TttTtatacctttCTtTaAC	577_10	-19.34	8120
  577	TTTTTATACCTTTCTTTAAC	2-3-1-7-2-2-3	TTtttAtacctttCTttAAC	577_11	-19.53	8120
  577	TTTTTATACCTTTCTTTAAC	1-1-2-9-1-1-1-1-3	TtTTtatacctttCtTtAAC	577_12	-18.84	8120
  577	TTTTTATACCTTTCTTTAAC	1-3-2-7-1-1-1-2-2	TtttTAtacctttCtTtaAC	577_13	-19.27	8120
  577	TTTTTATACCTTTCTTTAAC	3-1-1-8-1-2-1-1-2	TTTtTatacctttCttTaAC	577_14	-20.20	8120
  578	TTTTTTCTTACTATCTTCAA	1-5-1-7-2-2-2	TtttttCttactatCTtcAA	578_1	-19.02	8584
  578	TTTTTTCTTACTATCTTCAA	2-2-1-1-1-7-1-1-1-1-2	TTttTtCttactatCtTcAA	578_2	-19.31	8584
  578	TTTTTTCTTACTATCTTCAA	1-2-2-9-1-2-3	TttTTtcttactatCttCAA	578_3	-20.05	8584
  578	TTTTTTCTTACTATCTTCAA	1-1-1-1-1-1-1-7-1-3-2	TtTtTtCttactatCttcAA	578_4	-18.43	8584
  578	TTTTTTCTTACTATCTTCAA	3-3-1-8-1-2-2	TTTtttCttactatcTtcAA	578_5	-18.99	8584
  578	TTTTTTCTTACTATCTTCAA	2-1-2-1-1-8-1-2-2	TTtTTtCttactatcttcAA	578_6	-19.29	8584
  578	TTTTTTCTTACTATCTTCAA	1-1-3-1-1-9-1-1-2	TtTTTtCttactatctTcAA	578_7	-19.15	8584
  578	TTTTTTCTTACTATCTTCAA	2-1-1-11-1-1-3	TTtTttcttactatcTtCAA	578_8	-19.58	8584
  578	TTTTTTCTTACTATCTTCAA	1-4-1-10-4	TttttTcttactatctTCAA	578_9	-19.31	8584
  579	TTTTTTTCTTACTATCTTCA	1-12-1-1-1-2-2	TttttttcttactAtCttCA	579_1	-19.29	8585
  579	TTTTTTTCTTACTATCTTCA	2-1-1-9-1-4-2	TTtTtttcttactAtcttCA	579_2	-19.42	8585
  579	TTTTTTTCTTACTATCTTCA	1-1-1-2-1-7-1-4-2	TtTttTtcttactAtcttCA	579_3	-18.91	8585
  579	TTTTTTTCTTACTATCTTCA	1-1-2-9-1-2-1-1-2	TtTTtttcttactAtcTtCA	579_4	-19.94	8585
  579	TTTTTTTCTTACTATCTTCA	1-3-2-10-1-1-2	TttttTtcttactatcTtCA	579_5	-19.84	8585
  579	TTTTTTTCTTACTATCTTCA	2-3-1-12-2	TTtttTtcttactatcttCA	579_6	-19.33	8585
  579	TTTTTTTCTTACTATCTTCA	3-15-2	TTTttttcttactatcttCA	579_7	-19.84	8585
  579	TTTTTTTCTTACTATCTTCA	1-2-2-13-2	TttTTttcttactatcttCA	579_8	-19.33	8585
  579	TTTTTTTCTTACTATCTTCA	1-14-1-2-2	TttttttcttactatCttCA	579_9	-19.19	8585
  580	ATTTTTTTCTTACTATCTTC	1-4-1-8-1-1-1-1-2	AttttTttcttactAtCtTC	580_1	-18.09	8586
  580	ATTTTTTTCTTACTATCTTC	2-1-1-10-1-2-3	ATtTttttcttactAtcTTC	580_2	-19.39	8586
  580	ATTTTTTTCTTACTATCTTC	1-3-2-8-1-2-3	AtttTTttcttactAtcTTC	580_3	-18.95	8586
  580	ATTTTTTTCTTACTATCTTC	1-5-1-6-1-3-3	AtttttTtcttacTatcTTC	580_4	-18.98	8586
  580	ATTTTTTTCTTACTATCTTC	2-2-1-1-1-7-1-3-2	ATttTtTtcttactAtctTC	580_5	-18.66	8586
  580	ATTTTTTTCTTACTATCTTC	1-1-3-8-1-4-2	AtTTTtttcttacTatctTC	580_6	-19.58	8586
  580	ATTTTTTTCTTACTATCTTC	2-1-1-12-1-1-2	ATtTttttcttactatCtTC	580_7	-19.24	8586
  580	ATTTTTTTCTTACTATCTTC	1-1-1-2-1-11-3	AtTttTttcttactatcTTC	580_8	-18.34	8586
  580	ATTTTTTTCTTACTATCTTC	1-1-2-1-2-11-2	AtTTtTTtcttactatctTC	580_9	-18.94	8586
  581	AATTTTTTTCTTACTATCTT	1-4-1-7-1-1-1-1-3	AatttTtttcttaCtAtCTT	581_1	-18.53	8587
  581	AATTTTTTTCTTACTATCTT	1-3-1-1-1-6-2-3-2	AattTtTttcttaCTatcTT	581_2	-18.69	8587
  581	AATTTTTTTCTTACTATCTT	1-1-2-10-2-2-2	AaTTtttttcttacTAtcTT	581_3	-18.80	8587
  581	AATTTTTTTCTTACTATCTT	2-1-1-1-1-8-1-2-3	AAtTtTtttcttacTatCTT	581_4	-19.20	8587
  581	AATTTTTTTCTTACTATCTT	4-2-1-7-1-3-2	AATTtttttcttacTatcTT	581_5	-19.30	8587
  581	AATTTTTTTCTTACTATCTT	2-2-2-7-1-1-2-1-2	AAtttTtttcttaCtATcTT	581_6	-19.52	8587
  581	AATTTTTTTCTTACTATCTT	1-12-1-2-4	AatttttttcttaCtaTCTT	581_7	-19.25	8587
  581	AATTTTTTTCTTACTATCTT	1-1-4-7-1-4-2	AaTTTTtttcttaCtatcTT	581_8	-19.35	8587
  581	AATTTTTTTCTTACTATCTT	2-1-3-9-1-1-3	AAtTTTtttcttactAtCTT	581_9	-19.68	8587
  582	GTTTATACCCTTTCCAAT	1-1-1-1-1-7-2-2-2	GtTtAtacccttTCcaAT	582_1	-21.48	9209
  582	GTTTATACCCTTTCCAAT	1-12-2-1-2	GtttataccctttCCaAT	582_2	-22.28	9209
  582	GTTTATACCCTTTCCAAT	1-3-1-8-1-1-3	GtttAtaccctttCcAAT	582_3	-20.46	9209
  582	GTTTATACCCTTTCCAAT	1-1-1-1-1-9-1-1-2	GtTtAtaccctttcCaAT	582_4	-20.30	9209
  582	GTTTATACCCTTTCCAAT	2-11-1-2-2	GTttataccctttCcaAT	582_5	-21.64	9209
  582	GTTTATACCCTTTCCAAT	1-1-2-9-1-1-3	GtTTataccctttCcAAT	582_6	-21.90	9209
  582	GTTTATACCCTTTCCAAT	1-1-1-13-2	GtTtataccctttccaAT	582_7	-19.63	9209
  582	GTTTATACCCTTTCCAAT	1-2-1-12-2	GttTataccctttccaAT	582_8	-20.05	9209
  582	GTTTATACCCTTTCCAAT	1-13-4	GtttataccctttcCAAT	582_9	-21.59	9209
  583	TGTTTATACCCTTTCCAA	2-1-1-10-1-1-2	TGtTtataccctttCcAA	583_1	-21.08	9210
  583	TGTTTATACCCTTTCCAA	1-4-1-6-1-1-1-1-2	TgtttAtaccctTtCcAA	583_2	-19.97	9210
  583	TGTTTATACCCTTTCCAA	1-3-1-9-1-1-2	TgttTataccctttCcAA	583_3	-20.30	9210
  583	TGTTTATACCCTTTCCAA	2-1-1-1-1-6-1-3-2	TGtTtAtaccctTtccAA	583_4	-20.71	9210
  583	TGTTTATACCCTTTCCAA	1-2-1-8-1-2-3	TgtTtataccctTtcCAA	583_5	-21.40	9210
  583	TGTTTATACCCTTTCCAA	1-4-1-9-3	TgtttAtaccctttcCAA	583_6	-20.89	9210
  583	TGTTTATACCCTTTCCAA	1-1-2-12-2	TgTTtataccctttccAA	583_7	-20.27	9210
  583	TGTTTATACCCTTTCCAA	1-12-2-1-2	TgtttatacccttTCcAA	583_8	-20.56	9210
  583	TGTTTATACCCTTTCCAA	2-2-1-11-2	TGttTataccctttccAA	583_9	-20.74	9210
  584	CTGTTTATACCCTTTCCA	1-1-1-10-1-2-2	CtGtttataccctTtcCA	584_1	-22.45	9211
  584	CTGTTTATACCCTTTCCA	1-12-1-2-2	CtgtttataccctTtcCA	584_2	-22.14	9211
  584	CTGTTTATACCCTTTCCA	1-1-1-1-1-11-2	CtGtTtataccctttcCA	584_3	-22.45	9211
  584	CTGTTTATACCCTTTCCA	1-1-1-13-2	CtGtttataccctttcCA	584_4	-22.15	9211
  584	CTGTTTATACCCTTTCCA	1-2-1-12-2	CtgTttataccctttcCA	584_5	-22.50	9211
  584	CTGTTTATACCCTTTCCA	1-3-1-11-2	CtgtTtataccctttcCA	584_6	-22.14	9211
  584	CTGTTTATACCCTTTCCA	1-4-1-10-2	CtgttTataccctttcCA	584_7	-22.57	9211
  584	CTGTTTATACCCTTTCCA	1-15-2	CtgtttataccctttcCA	584_8	-21.84	9211
  585	AATTATTTATACACCATCAT	2-1-1-1-1-8-3-1-2	AAtTaTttatacacCATcAT	585_1	-20.76	11511
  585	AATTATTTATACACCATCAT	3-2-2-6-1-1-2-1-2	AATtaTTtatacaCcATcAT	585_2	-20.88	11511
  585	AATTATTTATACACCATCAT	1-4-1-7-2-1-1-1-2	AattaTttatacaCCaTcAT	585_3	-19.62	11511
  585	AATTATTTATACACCATCAT	1-3-1-1-1-6-1-3-3	AattAtTtatacaCcatCAT	585_4	-18.98	11511
  585	AATTATTTATACACCATCAT	1-2-3-7-1-1-1-2-2	AatTATttatacaCcAtcAT	585_5	-19.65	11511
  585	AATTATTTATACACCATCAT	1-1-2-11-1-1-3	AaTTatttatacaccAtCAT	585_6	-19.53	11511
  585	AATTATTTATACACCATCAT	2-2-1-9-1-1-4	AAttAtttatacacCaTCAT	585_7	-20.11	11511
  585	AATTATTTATACACCATCAT	3-1-2-8-1-2-3	AATTATttatacacCatCAT	585_8	-21.48	11511
  585	AATTATTTATACACCATCAT	4-2-1-7-1-3-2	AATTatTtatacacCatcAT	585_9	-19.60	11511
  585	AATTATTTATACACCATCAT	2-1-1-2-1-6-3-2-2	AAtTatTtatacaCCAtcAT	585_10	-21.69	11511
  585	AATTATTTATACACCATCAT	1-3-2-7-1-1-1-1-3	AattATttatacaCcAtCAT	585_11	-19.97	11511
  585	AATTATTTATACACCATCAT	2-1-3-8-1-1-1-1-2	AAtTATttatacacCaTcAT	585_12	-20.42	11511
  585	AATTATTTATACACCATCAT	1-1-2-1-1-8-1-2-3	AaTTaTttatacacCatCAT	585_13	-20.49	11511
  585	AATTATTTATACACCATCAT	2-1-1-2-1-9-4	AAtTatTtatacaccaTCAT	585_14	-20.47	11511
  586	AAATTATTTATACACCATCA	1-12-3-1-3	AaattatttatacACCaTCA	586_1	-20.58	11512
  586	AAATTATTTATACACCATCA	1-1-1-2-1-7-1-1-2-1-2	AaAttAtttatacAcCAtCA	586_2	-18.56	11512
  586	AAATTATTTATACACCATCA	3-2-2-6-2-3-2	AAAttATttatacACcatCA	586_3	-19.68	11512
  586	AAATTATTTATACACCATCA	4-10-1-2-3	AAATtatttatacaCcaTCA	586_4	-20.15	11512
  586	AAATTATTTATACACCATCA	1-1-4-8-1-1-1-1-2	AaATTAtttatacaCcAtCA	586_5	-20.72	11512
  586	AAATTATTTATACACCATCA	2-1-2-1-1-7-1-3-2	AAaTTaTttatacaCcatCA	586_6	-19.39	11512
  586	AAATTATTTATACACCATCA	1-3-2-7-1-1-1-1-3	AaatTAtttatacAcCaTCA	586_7	-19.65	11512
  586	AAATTATTTATACACCATCA	1-1-3-8-1-2-4	AaATTatttatacAccATCA	586_8	-20.88	11512
  586	AAATTATTTATACACCATCA	2-2-1-1-1-9-4	AAatTaTttatacaccATCA	586_9	-19.63	11512
  586	AAATTATTTATACACCATCA	1-1-1-1-1-1-1-6-3-2-2	AaAtTaTttatacACCatCA	586_10	-20.95	11512
  586	AAATTATTTATACACCATCA	1-3-2-7-1-1-2-1-2	AaatTAtttatacAcCAtCA	586_11	-20.00	11512
  586	AAATTATTTATACACCATCA	2-1-2-1-1-7-1-1-1-1-2	AAaTTaTttatacaCcAtCA	586_12	-19.44	11512
  586	AAATTATTTATACACCATCA	3-2-1-8-1-2-3	AAAttAtttatacaCcaTCA	586_13	-19.00	11512
  586	AAATTATTTATACACCATCA	1-1-4-9-1-1-3	AaATTAtttatacacCaTCA	586_14	-21.59	11512
  587	AAAATTATTTATACACCATC	2-3-1-7-1-1-5	AAaatTatttataCaCCATC	587_1	-21.17	11513
  587	AAAATTATTTATACACCATC	1-2-2-9-6	AaaATtatttatacACCATC	587_2	-21.34	11513
  587	AAAATTATTTATACACCATC	2-3-2-6-3-1-3	AAaatTAtttataCACcATC	587_3	-20.67	11513
  587	AAAATTATTTATACACCATC	3-1-1-1-1-7-3-1-2	AAAaTtAtttatacACCaTC	587_4	-19.11	11513
  587	AAAATTATTTATACACCATC	7-6-1-1-1-2-2	AAAATTAtttataCaCcaTC	587_5	-20.66	11513
  587	AAAATTATTTATACACCATC	1-1-1-1-2-8-2-1-3	AaAaTTatttatacACcATC	587_6	-18.20	11513
  587	AAAATTATTTATACACCATC	1-1-5-6-2-3-2	AaAATTAtttataCAccaTC	587_7	-20.71	11513
  587	AAAATTATTTATACACCATC	2-1-3-7-1-2-4	AAaATTatttataCacCATC	587_8	-20.87	11513
  587	AAAATTATTTATACACCATC	4-1-1-8-1-1-4	AAAAtTatttatacAcCATC	587_9	-19.30	11513
  587	AAAATTATTTATACACCATC	1-1-2-1-2-6-3-2-2	AaAAtTAtttataCACcaTC	587_10	-20.13	11513
  587	AAAATTATTTATACACCATC	1-2-3-7-1-1-2-1-2	AaaATTatttataCaCCaTC	587_11	-20.44	11513
  587	AAAATTATTTATACACCATC	3-1-2-7-1-2-4	AAAaTTatttataCacCATC	587_12	-20.27	11513
  587	AAAATTATTTATACACCATC	3-2-1-8-3-1-2	AAAatTatttatacACCaTC	587_13	-19.30	11513
  587	AAAATTATTTATACACCATC	2-1-3-8-2-1-3	AAaATTatttatacACcATC	587_14	-19.52	11513
  588	TAAAATTATTTATACACCAT	2-3-1-7-1-1-5	TAaaaTtatttatAcACCAT	588_1	-20.14	11514
  588	TAAAATTATTTATACACCAT	1-2-1-2-1-6-2-1-4	TaaAatTatttatACaCCAT	588_2	-20.15	11514
  588	TAAAATTATTTATACACCAT	1-1-1-1-2-8-1-1-4	TaAaATtatttataCaCCAT	588_3	-20.40	11514
  588	TAAAATTATTTATACACCAT	4-1-2-6-4-1-2	TAAAaTTatttatACACcAT	588_4	-21.36	11514
  588	TAAAATTATTTATACACCAT	1-3-3-6-3-1-3	TaaaATTatttatACAcCAT	588_5	-21.07	11514
  588	TAAAATTATTTATACACCAT	2-1-4-7-3-1-2	TAaAATTatttataCACcAT	588_6	-21.36	11514
  588	TAAAATTATTTATACACCAT	3-1-1-1-1-7-2-1-3	TAAaAtTatttataCAcCAT	588_7	-20.41	11514
  588	TAAAATTATTTATACACCAT	7-6-1-3-3	TAAAATTatttatAcacCAT	588_8	-20.85	11514
  588	TAAAATTATTTATACACCAT	2-1-2-11-4	TAaAAttatttatacaCCAT	588_9	-19.82	11514
  588	TAAAATTATTTATACACCAT	2-2-3-6-4-1-2	TAaaATTatttatACACcAT	588_10	-21.41	11514
  588	TAAAATTATTTATACACCAT	1-1-1-1-3-6-1-2-4	TaAaATTatttatAcaCCAT	588_11	-21.15	11514
  588	TAAAATTATTTATACACCAT	2-1-2-1-1-7-2-1-3	TAaAAtTatttataCAcCAT	588_12	-20.41	11514
  588	TAAAATTATTTATACACCAT	3-2-2-7-1-1-4	TAAaaTTatttataCaCCAT	588_13	-21.86	11514
  588	TAAAATTATTTATACACCAT	1-1-2-1-1-9-5	TaAAaTtatttatacACCAT	588_14	-19.68	11514
  589	TAAAATTATTTATACACCA	1-1-2-1-1-7-6	TaAAaTtatttatACACCA	589_1	-20.31	11515
  589	TAAAATTATTTATACACCA	1-2-3-6-1-1-5	TaaAATtatttaTaCACCA	589_2	-21.36	11515
  589	TAAAATTATTTATACACCA	2-3-1-7-6	TAaaaTtatttatACACCA	589_3	-20.58	11515
  589	TAAAATTATTTATACACCA	3-1-2-6-4-1-2	TAAaATtatttaTACAcCA	589_4	-21.36	11515
  589	TAAAATTATTTATACACCA	4-1-1-6-2-2-3	TAAAaTtatttaTAcaCCA	589_5	-20.51	11515
  589	TAAAATTATTTATACACCA	2-1-2-7-1-1-1-1-3	TAaAAttatttaTaCaCCA	589_6	-19.30	11515
  589	TAAAATTATTTATACACCA	1-3-2-6-2-2-3	TaaaATtatttaTAcaCCA	589_7	-19.40	11515
  589	TAAAATTATTTATACACCA	5-8-2-1-3	TAAAAttatttatACaCCA	589_8	-19.77	11515
  589	TAAAATTATTTATACACCA	3-1-2-9-4	TAAaATtatttatacACCA	589_9	-19.55	11515
  589	TAAAATTATTTATACACCA	2-1-3-6-4-1-2	TAaAATtatttaTACAcCA	589_10	-21.36	11515
  589	TAAAATTATTTATACACCA	3-1-2-6-3-1-3	TAAaATtatttaTACaCCA	589_11	-22.18	11515
  589	TAAAATTATTTATACACCA	1-1-3-7-2-1-4	TaAAAttatttaTAcACCA	589_12	-19.78	11515
  589	TAAAATTATTTATACACCA	2-2-1-7-1-1-1-1-3	TAaaAttatttaTaCaCCA	589_13	-18.76	11515
  589	TAAAATTATTTATACACCA	4-1-1-8-5	TAAAaTtatttataCACCA	589_14	-21.06	11515
  590	ATATTGATTCAATTCCC	2-9-2-1-3	ATattgattcaATtCCC	590_1	-21.84	13226
  590	ATATTGATTCAATTCCC	1-2-1-7-6	AtaTtgattcaATTCCC	590_2	-22.10	13226
  590	ATATTGATTCAATTCCC	2-9-1-1-1-1-2	ATattgattcaAtTcCC	590_3	-18.59	13226
  590	ATATTGATTCAATTCCC	1-1-2-8-5	AtATtgattcaaTTCCC	590_4	-21.87	13226
  590	ATATTGATTCAATTCCC	1-2-2-7-2-1-2	AtaTTgattcaaTTcCC	590_5	-19.29	13226
  590	ATATTGATTCAATTCCC	1-3-1-6-2-2-2	AtatTgattcaATtcCC	590_6	-18.59	13226
  590	ATATTGATTCAATTCCC	1-2-2-6-1-2-3	AtaTTgattcaAttCCC	590_7	-20.66	13226
  590	ATATTGATTCAATTCCC	1-1-1-1-1-7-1-1-3	AtAtTgattcaaTtCCC	590_8	-19.92	13226
  590	ATATTGATTCAATTCCC	1-1-1-8-1-2-3	AtAttgattcaAttCCC	590_9	-19.01	13226
  590	ATATTGATTCAATTCCC	4-7-1-3-2	ATATtgattcaAttcCC	590_10	-20.60	13226
  590	ATATTGATTCAATTCCC	3-1-1-7-1-2-2	ATAtTgattcaaTtcCC	590_11	-20.26	13226
  590	ATATTGATTCAATTCCC	1-3-1-8-4	AtatTgattcaatTCCC	590_12	-20.37	13226
  590	ATATTGATTCAATTCCC	2-1-1-10-3	ATaTtgattcaattCCC	590_13	-20.71	13226
  590	ATATTGATTCAATTCCC	2-2-1-9-3	ATatTgattcaattCCC	590_14	-21.06	13226
  590	ATATTGATTCAATTCCC	1-1-3-10-2	AtATTgattcaattcCC	590_15	-18.87	13226
  590	ATATTGATTCAATTCCC	2-2-1-6-2-2-2	ATatTgattcaATtcCC	590_16	-20.26	13226
  590	ATATTGATTCAATTCCC	3-8-1-1-4	ATAttgattcaAtTCCC	590_17	-22.71	13226
  590	ATATTGATTCAATTCCC	1-1-3-6-1-2-3	AtATTgattcaAttCCC	590_18	-21.57	13226
  590	ATATTGATTCAATTCCC	1-1-1-1-1-7-5	AtAtTgattcaaTTCCC	590_19	-21.42	13226
  590	ATATTGATTCAATTCCC	2-1-1-8-1-1-3	ATaTtgattcaaTtCCC	590_20	-21.15	13226
  591	GCACATTCTTTCTATACCT	1-1-1-1-1-12-2	GcAcAttctttctatacCT	591_1	-21.27	15113
  591	GCACATTCTTTCTATACCT	1-3-1-12-2	GcacAttctttctatacCT	591_2	-21.12	15113
  592	GCACATTCTTTCTATACC	1-12-1-2-2	GcacattctttctAtaCC	592_1	-20.07	15114
  592	GCACATTCTTTCTATACC	1-1-1-1-1-11-2	GcAcAttctttctataCC	592_2	-20.17	15114
  592	GCACATTCTTTCTATACC	1-3-1-11-2	GcacAttctttctataCC	592_3	-20.02	15114
  592	GCACATTCTTTCTATACC	1-1-2-11-3	GcACattctttctatACC	592_4	-21.80	15114
  592	GCACATTCTTTCTATACC	1-1-1-1-2-7-1-1-3	GcAcATtctttctAtACC	592_5	-22.11	15114
  592	GCACATTCTTTCTATACC	1-1-1-1-2-7-1-2-2	GcAcATtctttctAtaCC	592_6	-21.51	15114
  592	GCACATTCTTTCTATACC	1-15-2	GcacattctttctataCC	592_7	-19.97	15114
  592	GCACATTCTTTCTATACC	1-4-1-9-3	GcacaTtctttctatACC	592_8	-21.01	15114
  592	GCACATTCTTTCTATACC	1-4-1-10-2	GcacaTtctttctataCC	592_9	-20.41	15114
  592	GCACATTCTTTCTATACC	2-11-1-2-2	GCacattctttctAtaCC	592_10	-22.39	15114
  592	GCACATTCTTTCTATACC	1-1-1-1-1-8-1-2-2	GcAcAttctttctAtaCC	592_11	-20.27	15114
  592	GCACATTCTTTCTATACC	1-3-1-9-1-1-2	GcacAttctttctaTaCC	592_12	-20.89	15114
  592	GCACATTCTTTCTATACC	1-1-1-1-1-10-3	GcAcAttctttctatACC	592_13	-20.77	15114
  592	GCACATTCTTTCTATACC	1-1-1-2-1-10-2	GcAcaTtctttctataCC	592_14	-20.56	15114
  593	TTATTTCCATTTATTTTCA	1-1-1-1-1-8-3-1-2	TtAtTtccatttaTTTtCA	593_1	-19.10	15563
  593	TTATTTCCATTTATTTTCA	1-2-2-7-1-1-1-1-3	TtaTTtccatttAtTtTCA	593_2	-19.27	15563
  593	TTATTTCCATTTATTTTCA	2-2-1-8-1-1-1-1-2	TTatTtccatttaTtTtCA	593_3	-18.92	15563
  593	TTATTTCCATTTATTTTCA	1-1-2-9-1-2-3	TtATttccatttaTttTCA	593_4	-19.41	15563
  594	TTTATTTCCATTTATTTTCA	1-1-1-11-1-2-3	TtTatttccatttaTttTCA	594_1	-19.80	15563
  594	TTTATTTCCATTTATTTTCA	1-4-1-7-1-1-1-2-2	TttatTtccatttAtTttCA	594_2	-18.34	15563
  594	TTTATTTCCATTTATTTTCA	1-3-2-9-2-1-2	TttaTTtccatttatTTtCA	594_3	-20.01	15563
  594	TTTATTTCCATTTATTTTCA	2-1-1-1-1-8-1-1-1-1-2	TTTAtTtccatttaTtTtCA	594_4	-19.60	15563
  595	ATTTATTTCCATTTATTTTC	1-1-1-2-1-8-3-1-2	AtTtaTttccatttATTtTC	595_1	-19.05	15564
  595	ATTTATTTCCATTTATTTTC	1-3-2-7-1-3-3	AtttATttccattTattTTC	595_2	-19.03	15564
  595	ATTTATTTCCATTTATTTTC	1-1-2-10-1-2-3	AtTTatttccatttAttTTC	595_3	-18.60	15564
  595	ATTTATTTCCATTTATTTTC	2-1-1-1-1-8-1-1-1-1-2	ATtTaTttccatttAtTtTC	595_4	-18.96	15564
  596	TTTATTTCCATTTATTTTC	1-1-1-1-1-8-2-1-3	TtTaTttccatttATtTTC	596_1	-18.66	15564
  596	TTTATTTCCATTTATTTTC	3-2-1-7-3-1-2	TTTatTtccatttATTtTC	596_2	-19.84	15564
  596	TTTATTTCCATTTATTTTC	2-2-2-7-1-1-4	TTtaTTtccatttAtTTTC	596_3	-19.12	15564
  596	TTTATTTCCATTTATTTTC	5-7-1-3-3	TTTATttccattTattTTC	596_4	-21.30	15564
  597	CCATTTATTTCCATTTATTT	1-1-1-11-2-2-2	CcAtttatttccatTTatTT	597_1	-19.89	15566
  597	CCATTTATTTCCATTTATTT	1-3-1-9-1-1-1-1-2	CcatTtatttccatTtAtTT	597_2	-19.00	15566
  597	CCATTTATTTCCATTTATTT	1-1-1-2-1-8-1-2-3	CcAttTatttccatTtaTTT	597_3	-20.33	15566
  597	CCATTTATTTCCATTTATTT	1-2-2-1-1-11-2	CcaTTTAtttccatttatTT	597_4	-19.64	15566
  598	TCCATTTATTTCCATTTATT	2-11-2-3-2	TCcatttatttccATttaTT	598_1	-21.22	15567
  598	TCCATTTATTTCCATTTATT	2-2-1-8-1-1-1-2-2	TCcaTttatttccAtTtaTT	598_2	-20.71	15567
  598	TCCATTTATTTCCATTTATT	1-1-2-9-1-4-2	TcCAtttatttccAtttaTT	598_3	-20.63	15567
  598	TCCATTTATTTCCATTTATT	2-1-1-1-1-11-3	TCcAtTtatttccatttATT	598_4	-21.18	15567
  599	TCCATTTATTTCCATTTAT	2-11-2-2-2	TCcatttatttccATttAT	599_1	-20.30	15568
  599	TCCATTTATTTCCATTTAT	2-2-1-8-1-1-1-1-2	TCcaTttatttccAtTTAT	599_2	-19.80	15568
  599	TCCATTTATTTCCATTTAT	1-1-2-9-1-3-2	TcCAtttatttccAtttAT	599_3	-19.72	15568
  599	TCCATTTATTTCCATTTAT	1-1-1-1-2-7-1-3-2	TcCaTTtatttccAtttAT	599_4	-19.50	15568
  600	TTCCATTTATTTCCATTTAT	1-1-1-2-1-8-1-1-1-1-2	TtCcaTttatttccAtTtAT	600_1	-20.12	15568
  600	TTCCATTTATTTCCATTTAT	1-3-1-10-2-1-2	TtccAtttatttccaTTTAT	600_2	-19.86	15568
  600	TTCCATTTATTTCCATTTAT	1-1-1-3-1-7-1-3-2	TtCcatTtatttccAtttAT	600_3	-19.68	15568
  600	TTCCATTTATTTCCATTTAT	1-1-1-1-2-8-1-3-2	TtCcATttatttccAtttAT	600_4	-20.68	15568
  601	TTTCCATTTATTTCCATTTA	1-4-1-7-1-2-1-1-2	TttccAtttatttCcaTtTA	601_1	-20.53	15569
  601	TTTCCATTTATTTCCATTTA	2-2-1-12-3	TTtcCatttatttccatTTA	601_2	-21.47	15569
  601	TTTCCATTTATTTCCATTTA	1-2-1-2-1-8-1-2-2	TttCcaTttatttccAttTA	601_3	-20.53	15569
  601	TTTCCATTTATTTCCATTTA	1-4-1-9-1-2-2	TttccAtttatttccAttTA	601_4	-19.37	15569
  602	CTTTCCATTTATTTCCATT	1-11-1-1-1-1-3	CtttccatttatTtCcATT	602_1	-21.20	15571
  602	CTTTCCATTTATTTCCATT	2-2-1-9-1-2-2	CTttCcatttatttCcaTT	602_2	-22.00	15571
  602	CTTTCCATTTATTTCCATT	1-4-1-9-1-1-2	CtttcCatttatttcCaTT	602_3	-20.42	15571
  602	CTTTCCATTTATTTCCATT	1-3-1-11-3	CtttCcatttatttccATT	602_4	-20.89	15571
  603	ATCTTTCCATTTATTTCCAT	1-2-1-12-1-1-2	AtcTttccatttatttCcAT	603_1	-21.24	15572
  603	ATCTTTCCATTTATTTCCAT	1-3-1-1-1-7-1-3-2	AtctTtCcatttatTtccAT	603_2	-21.33	15572
  603	ATCTTTCCATTTATTTCCAT	1-5-1-6-1-4-2	AtctttCcatttaTttccAT	603_3	-21.16	15572
  603	ATCTTTCCATTTATTTCCAT	1-16-3	AtctttccatttatttcCAT	603_4	-21.95	15572
  604	TCTTTCCATTTATTTCCAT	2-13-1-1-2	TCtttccatttatttCcAT	604_1	-21.57	15572
  604	TCTTTCCATTTATTTCCAT	1-2-1-1-1-7-1-1-1-1-2	TctTtCcatttatTtCcAT	604_2	-21.35	15572
  604	TCTTTCCATTTATTTCCAT	2-14-3	TCtttccatttatttcCAT	604_3	-22.80	15572
  604	TCTTTCCATTTATTTCCAT	2-3-1-11-2	TCtttCcatttatttccAT	604_4	-21.57	15572
  605	ATCTTTCCATTTATTTCCA	1-2-1-10-1-2-2	AtcTttccatttatTtcCA	605_1	-20.70	15573
  605	ATCTTTCCATTTATTTCCA	1-3-1-8-1-3-2	AtctTtccatttaTttcCA	605_2	-20.63	15573
  605	ATCTTTCCATTTATTTCCA	1-1-1-14-2	AtCtttccatttatttcCA	605_3	-20.86	15573
  605	ATCTTTCCATTTATTTCCA	1-4-1-9-1-1-2	AtcttTccatttattTcCA	605_4	-20.63	15573
  606	TATCTTTCCATTTATTTCCA	1-4-1-8-2-2-2	TatctTtccatttaTTtcCA	606_1	-22.54	15573
  606	TATCTTTCCATTTATTTCCA	2-16-2	TAtctttccatttatttcCA	606_2	-22.12	15573
  606	TATCTTTCCATTTATTTCCA	1-2-1-14-2	TatCtttccatttatttcCA	606_3	-21.97	15573
  606	TATCTTTCCATTTATTTCCA	1-17-2	TatctttccatttatttcCA	606_4	-20.99	15573
  607	TATCTTTCCATTTATTTCC	2-12-1-2-2	TAtctttccatttaTttCC	607_1	-21.63	15574
  607	TATCTTTCCATTTATTTCC	1-2-1-13-2	TatCtttccatttatttCC	607_2	-21.04	15574
  607	TATCTTTCCATTTATTTCC	1-2-2-12-2	TatCTttccatttatttCC	607_3	-22.23	15574
  607	TATCTTTCCATTTATTTCC	1-4-1-9-1-1-2	TatctTtccatttatTtCC	607_4	-20.66	15574
  608	AAATCTCAACTACCATTTTT	1-1-1-3-1-7-3-1-2	AaAtctCaactaccATTtTT	608_1	-19.53	25248
  608	AAATCTCAACTACCATTTTT	3-1-1-9-2-1-3	AAAtCtcaactaccATtTTT	608_2	-20.58	25248
  608	AAATCTCAACTACCATTTTT	1-3-1-8-1-1-5	AaatCtcaactacCaTTTTT	608_3	-20.56	25248
  608	AAATCTCAACTACCATTTTT	1-1-1-2-1-7-2-2-3	AaAtcTcaactacCAttTTT	608_4	-20.20	25248
  608	AAATCTCAACTACCATTTTT	1-3-1-1-1-6-1-1-1-2-2	AaatCtCaactacCaTttTT	608_5	-19.10	25248
  608	AAATCTCAACTACCATTTTT	2-3-2-6-1-2-4	AAatcTCaactacCatTTTT	608_6	-21.04	25248
  608	AAATCTCAACTACCATTTTT	2-1-2-1-1-7-1-3-2	AAaTCtCaactaccAtttTT	608_7	-19.79	25248
  608	AAATCTCAACTACCATTTTT	1-1-3-11-1-1-2	AaATCtcaactaccatTtTT	608_8	-19.97	25248
  608	AAATCTCAACTACCATTTTT	3-1-1-1-1-10-3	AAAtCtCaactaccattTTT	608_9	-19.95	25248
  609	AAAATCTCAACTACCATTTT	1-12-4-1-2	AaaatctcaactaCCATtTT	609_1	-21.31	25249
  609	AAAATCTCAACTACCATTTT	3-11-2-1-3	AAAatctcaactacCAtTTT	609_2	-19.57	25249
  609	AAAATCTCAACTACCATTTT	2-1-1-1-1-8-2-1-3	AAaAtCtcaactacCAtTTT	609_3	-20.33	25249
  609	AAAATCTCAACTACCATTTT	1-1-4-9-1-2-2	AaAATCtcaactaccAttTT	609_4	-19.46	25249
  609	AAAATCTCAACTACCATTTT	1-1-2-2-1-7-2-2-2	AaAAtcTcaactacCAttTT	609_5	-19.13	25249
  609	AAAATCTCAACTACCATTTT	4-1-1-7-1-2-4	AAAAtCtcaactaCcaTTTT	609_6	-20.75	25249
  609	AAAATCTCAACTACCATTTT	1-1-1-2-1-8-1-1-4	AaAatCtcaactacCaTTTT	609_7	-19.30	25249
  609	AAAATCTCAACTACCATTTT	1-2-3-7-1-1-1-1-3	AaaATCtcaactaCcAtTTT	609_8	-20.51	25249
  609	AAAATCTCAACTACCATTTT	2-2-2-10-1-1-2	AAaaTCtcaactaccaTtTT	609_9	-18.72	25249
  610	AAAATCTCAACTACCATTT	1-4-1-6-4-1-2	AaaatCtcaactACCAtTT	610_1	-20.63	25250
  610	AAAATCTCAACTACCATTT	3-10-6	AAAatctcaactaCCATTT	610_2	-21.90	25250
  610	AAAATCTCAACTACCATTT	6-6-2-2-3	AAAATCtcaactACcaTTT	610_3	-21.46	25250
  610	AAAATCTCAACTACCATTT	2-2-2-7-2-1-3	AAaaTCtcaactaCCaTTT	610_4	-21.18	25250
  610	AAAATCTCAACTACCATTT	6-7-2-2-2	AAAATCtcaactaCCatTT	610_5	-22.10	25250
  610	AAAATCTCAACTACCATTT	2-1-1-1-1-8-5	AAaAtCtcaactacCATTT	610_6	-20.27	25250
  610	AAAATCTCAACTACCATTT	1-1-1-1-2-8-5	AaAaTCtcaactacCATTT	610_7	-20.88	25250
  610	AAAATCTCAACTACCATTT	1-1-2-1-1-8-2-1-2	AaAAtCtcaactacCAtTT	610_8	-18.51	25250
  610	AAAATCTCAACTACCATTT	6-9-4	AAAATCtcaactaccATTT	610_9	-20.94	25250
  611	GAAAATCTCAACTACCATT	1-1-3-7-1-2-4	GaAAAtctcaacTacCATT	611_1	-20.48	25251
  611	GAAAATCTCAACTACCATT	1-1-2-8-1-1-1-1-3	GaAAatctcaacTaCcATT	611_2	-18.75	25251
  611	GAAAATCTCAACTACCATT	3-1-1-10-4	GAAaAtctcaactacCATT	611_3	-20.73	25251
  611	GAAAATCTCAACTACCATT	2-1-2-10-4	GAaAAtctcaactacCATT	611_4	-20.73	25251
  611	GAAAATCTCAACTACCATT	2-2-1-7-1-4-2	GAaaAtctcaacTaccaTT	611_5	-18.28	25251
  611	GAAAATCTCAACTACCATT	2-12-5	GAaaatctcaactaCCATT	611_6	-22.25	25251
  611	GAAAATCTCAACTACCATT	4-10-2-1-2	GAAAatctcaactaCCaTT	611_7	-21.06	25251
  611	GAAAATCTCAACTACCATT	4-10-1-1-3	GAAAatctcaactaCcATT	611_8	-19.73	25251
  611	GAAAATCTCAACTACCATT	5-12-2	GAAAAtctcaactaccaTT	611_9	-18.61	25251
  612	TGAAAATCTCAACTACCAT	1-4-1-6-1-1-2-1-2	TgaaaAtctcaaCtACcAT	612_1	-18.43	25252
  612	TGAAAATCTCAACTACCAT	2-1-2-7-1-2-1-1-2	TGaAAatctcaaCtaCcAT	612_2	-19.46	25252
  612	TGAAAATCTCAACTACCAT	1-1-2-8-1-2-1-1-2	TgAAaatctcaaCtaCcAT	612_3	-18.58	25252
  612	TGAAAATCTCAACTACCAT	1-2-1-1-1-6-1-3-3	TgaAaAtctcaaCtacCAT	612_4	-19.40	25252
  612	TGAAAATCTCAACTACCAT	1-3-2-10-3	TgaaAAtctcaactacCAT	612_5	-18.60	25252
  612	TGAAAATCTCAACTACCAT	1-11-1-2-4	TgaaaatctcaaCtaCCAT	612_6	-21.11	25252
  612	TGAAAATCTCAACTACCAT	3-1-2-6-1-4-2	TGAaAAtctcaaCtaccAT	612_7	-20.39	25252
  612	TGAAAATCTCAACTACCAT	1-1-1-1-1-7-1-3-3	TgAaAatctcaaCtacCAT	612_8	-19.60	25252
  612	TGAAAATCTCAACTACCAT	4-12-3	TGAAaatctcaactacCAT	612_9	-21.07	25252
  613	ATCATTCTCAACAATTAAA	4-8-7	ATCAttctcaacAATTAAA	613_1	-20.89	30599
  613	ATCATTCTCAACAATTAAA	1-1-4-6-7	AtCATTctcaacAATTAAA	613_2	-21.09	30599
  613	ATCATTCTCAACAATTAAA	5-7-2-1-1-1-2	ATCATtctcaacAAtTaAA	613_3	-19.03	30599
  613	ATCATTCTCAACAATTAAA	5-8-2-2-2	ATCATtctcaacaATtaAA	613_4	-19.28	30599
  613	ATCATTCTCAACAATTAAA	4-1-1-8-5	ATCAtTctcaacaaTTAAA	613_5	-19.86	30599
  613	ATCATTCTCAACAATTAAA	5-7-4-1-2	ATCATtctcaacAATTaAA	613_6	-20.79	30599
  613	ATCATTCTCAACAATTAAA	4-8-1-1-5	ATCAttctcaacAaTTAAA	613_7	-19.56	30599
  613	ATCATTCTCAACAATTAAA	1-1-4-6-1-1-5	AtCATTctcaacAaTTAAA	613_8	-19.76	30599
  613	ATCATTCTCAACAATTAAA	4-1-1-7-3-1-2	ATCAtTctcaacaATTaAA	613_9	-19.64	30599
  613	ATCATTCTCAACAATTAAA	5-8-1-1-4	ATCATtctcaacaAtTAAA	613_10	-20.11	30599
  614	ATCATTCTCAACAATTAA	4-8-6	ATCAttctcaacAATTAA	614_1	-20.14	30600
  614	ATCATTCTCAACAATTAA	1-1-4-6-6	AtCATTctcaacAATTAA	614_2	-20.34	30600
  614	ATCATTCTCAACAATTAA	5-8-1-1-3	ATCATtctcaacaAtTAA	614_3	-19.36	30600
  614	ATCATTCTCAACAATTAA	4-8-1-1-4	ATCAttctcaacAaTTAA	614_4	-18.81	30600
  614	ATCATTCTCAACAATTAA	5-8-5	ATCATtctcaacaATTAA	614_5	-21.12	30600
  614	ATCATTCTCAACAATTAA	5-7-1-2-3	ATCATtctcaacAatTAA	614_6	-19.11	30600
  614	ATCATTCTCAACAATTAA	3-10-5	ATCattctcaacaATTAA	614_7	-18.40	30600
  614	ATCATTCTCAACAATTAA	4-9-1-1-3	ATCAttctcaacaAtTAA	614_8	-18.11	30600
  614	ATCATTCTCAACAATTAA	4-1-1-8-4	ATCAtTctcaacaaTTAA	614_9	-19.11	30600
  614	ATCATTCTCAACAATTAA	1-1-3-9-4	AtCATtctcaacaaTTAA	614_10	-18.05	30600
  615	GATCATTCTCAACAATTAA	2-3-1-6-2-1-4	GAtcaTtctcaaCAaTTAA	615_1	-20.54	30600
  615	GATCATTCTCAACAATTAA	1-2-2-7-1-2-4	GatCAttctcaaCaaTTAA	615_2	-19.04	30600
  615	GATCATTCTCAACAATTAA	2-1-3-6-3-2-2	GAtCATtctcaaCAAttAA	615_3	-21.29	30600
  615	GATCATTCTCAACAATTAA	2-1-2-8-2-1-3	GAtCAttctcaacAAtTAA	615_4	-19.70	30600
  615	GATCATTCTCAACAATTAA	5-8-1-1-1-1-2	GATCAttctcaacAaTtAA	615_5	-19.79	30600
  615	GATCATTCTCAACAATTAA	4-8-3-2-2	GATCattctcaaCAAttAA	615_6	-20.50	30600
  615	GATCATTCTCAACAATTAA	1-2-3-6-2-2-3	GatCATtctcaaCAatTAA	615_7	-20.82	30600
  615	GATCATTCTCAACAATTAA	2-2-2-6-1-1-5	GAtcATtctcaaCaATTAA	615_8	-21.04	30600
  615	GATCATTCTCAACAATTAA	2-1-1-8-1-2-4	GAtCattctcaaCaaTTAA	615_9	-19.28	30600
  615	GATCATTCTCAACAATTAA	1-1-3-9-1-1-3	GaTCAttctcaacaAtTAA	615_10	-18.85	30600
  616	AGATCATTCTCAACAATTA	1-1-1-2-1-7-3-1-2	AgAtcAttctcaaCAAtTA	616_1	-19.10	30601
  616	AGATCATTCTCAACAATTA	1-3-1-8-2-1-3	AgatCattctcaaCAaTTA	616_2	-19.65	30601
  616	AGATCATTCTCAACAATTA	1-3-2-6-1-1-1-2-2	AgatCAttctcaAcAatTA	616_3	-18.49	30601
  616	AGATCATTCTCAACAATTA	1-1-1-1-2-11-2	AgAtCAttctcaacaatTA	616_4	-18.49	30601
  616	AGATCATTCTCAACAATTA	1-1-1-2-1-9-4	AgAtcAttctcaacaATTA	616_5	-18.49	30601
  616	AGATCATTCTCAACAATTA	1-3-2-6-1-1-5	AgatCAttctcaAcAATTA	616_6	-20.76	30601
  616	AGATCATTCTCAACAATTA	2-2-1-8-3-1-2	AGatCattctcaaCAAtTA	616_7	-20.47	30601
  616	AGATCATTCTCAACAATTA	3-2-1-7-1-2-3	AGAtcAttctcaaCaaTTA	616_8	-20.51	30601
  616	AGATCATTCTCAACAATTA	1-2-3-7-1-3-2	AgaTCAttctcaaCaatTA	616_9	-19.80	30601
  616	AGATCATTCTCAACAATTA	1-1-1-1-2-8-2-1-2	AgAtCAttctcaacAAtTA	616_10	-19.08	30601
  617	GATCATTCTCAACAATTA	2-3-1-6-6	GAtcaTtctcaaCAATTA	617_1	-21.11	30601
  617	GATCATTCTCAACAATTA	2-1-2-8-5	GAtCAttctcaacAATTA	617_2	-20.71	30601
  617	GATCATTCTCAACAATTA	2-2-2-6-2-2-2	GAtcATtctcaaCAatTA	617_3	-19.70	30601
  617	GATCATTCTCAACAATTA	1-1-3-7-1-1-1-1-2	GaTCAttctcaaCaAtTA	617_4	-18.78	30601
  617	GATCATTCTCAACAATTA	2-1-2-10-3	GAtCAttctcaacaaTTA	617_5	-19.31	30601
  617	GATCATTCTCAACAATTA	2-1-1-1-1-6-3-1-2	GAtCaTtctcaaCAAtTA	617_6	-20.02	30601
  617	GATCATTCTCAACAATTA	2-1-2-7-2-2-2	GAtCAttctcaaCAatTA	617_7	-20.53	30601
  617	GATCATTCTCAACAATTA	2-1-3-6-1-2-3	GAtCATtctcaaCaaTTA	617_8	-21.24	30601
  617	GATCATTCTCAACAATTA	2-2-1-8-5	GAtcAttctcaacAATTA	617_9	-18.63	30601
  617	GATCATTCTCAACAATTA	1-1-3-9-1-1-2	GaTCAttctcaacaAtTA	617_10	-18.10	30601
  618	AGATCATTCTCAACAATT	1-3-2-6-6	AgatCAttctcaACAATT	618_1	-21.03	30602
  618	AGATCATTCTCAACAATT	1-1-1-1-2-7-5	AgAtCAttctcaaCAATT	618_2	-20.70	30602
  618	AGATCATTCTCAACAATT	1-1-4-6-1-3-2	AgATCAttctcaAcaaTT	618_3	-19.56	30602
  618	AGATCATTCTCAACAATT	3-1-1-9-4	AGAtCattctcaacAATT	618_4	-19.61	30602
  618	AGATCATTCTCAACAATT	2-1-3-10-2	AGaTCAttctcaacaaTT	618_5	-19.09	30602
  618	AGATCATTCTCAACAATT	1-2-3-6-1-3-2	AgaTCAttctcaAcaaTT	618_6	-18.25	30602
  618	AGATCATTCTCAACAATT	2-2-2-7-2-1-2	AGatCAttctcaaCAaTT	618_7	-20.14	30602
  618	AGATCATTCTCAACAATT	1-1-1-1-2-7-1-1-3	AgAtCAttctcaaCaATT	618_8	-19.02	30602
  618	AGATCATTCTCAACAATT	1-2-3-8-4	AgaTCAttctcaacAATT	618_9	-19.23	30602
  618	AGATCATTCTCAACAATT	3-1-1-10-3	AGAtCattctcaacaATT	618_10	-19.34	30602
  619	GATCATTCTCAACAATT	2-1-2-6-6	GAtCAttctcaACAATT	619_1	-21.40	30602
  619	GATCATTCTCAACAATT	1-1-3-7-5	GaTCAttctcaaCAATT	619_2	-19.99	30602
  619	GATCATTCTCAACAATT	5-7-1-2-2	GATCAttctcaaCaaTT	619_3	-19.69	30602
  619	GATCATTCTCAACAATT	5-6-1-1-4	GATCAttctcaAcAATT	619_4	-20.83	30602
  619	GATCATTCTCAACAATT	2-1-2-7-5	GAtCAttctcaaCAATT	619_5	-20.57	30602
  619	GATCATTCTCAACAATT	5-6-1-3-2	GATCAttctcaAcaaTT	619_6	-19.43	30602
  619	GATCATTCTCAACAATT	4-8-5	GATCattctcaaCAATT	619_7	-21.04	30602
  619	GATCATTCTCAACAATT	1-1-3-7-2-1-2	GaTCAttctcaaCAaTT	619_8	-18.67	30602
  619	GATCATTCTCAACAATT	5-7-1-1-3	GATCAttctcaaCaATT	619_9	-20.82	30602
  619	GATCATTCTCAACAATT	2-1-2-8-4	GAtCAttctcaacAATT	619_10	-18.48	30602
  620	AAGATCATTCTCAACAAT	4-1-1-6-1-1-4	AAGAtCattctcAaCAAT	620_1	-20.71	30603
  620	AAGATCATTCTCAACAAT	4-9-5	AAGAtcattctcaACAAT	620_2	-20.79	30603
  620	AAGATCATTCTCAACAAT	2-2-2-6-6	AAgaTCattctcAACAAT	620_3	-19.88	30603
  620	AAGATCATTCTCAACAAT	4-1-1-7-2-1-2	AAGAtCattctcaACaAT	620_4	-19.77	30603
  620	AAGATCATTCTCAACAAT	2-1-3-8-4	AAgATCattctcaaCAAT	620_5	-20.10	30603
  620	AAGATCATTCTCAACAAT	4-1-1-6-2-2-2	AAGAtCattctcAAcaAT	620_6	-18.96	30603
  620	AAGATCATTCTCAACAAT	3-1-2-6-1-1-4	AAGaTCattctcAaCAAT	620_7	-20.12	30603
  620	AAGATCATTCTCAACAAT	2-1-3-6-1-1-4	AAgATCattctcAaCAAT	620_8	-20.17	30603
  620	AAGATCATTCTCAACAAT	1-1-1-2-1-7-5	AaGatCattctcaACAAT	620_9	-18.21	30603
  620	AAGATCATTCTCAACAAT	4-1-1-8-4	AAGAtCattctcaaCAAT	620_10	-20.63	30603
  621	AAAGATCATTCTCAACAA	1-1-1-9-6	AaAgatcattctCAACAA	621_1	-18.13	30604
  621	AAAGATCATTCTCAACAA	1-1-3-7-2-1-3	AaAGAtcattctCAaCAA	621_2	-20.08	30604
  621	AAAGATCATTCTCAACAA	1-3-2-6-2-1-3	AaagATcattctCAaCAA	621_3	-18.11	30604
  621	AAAGATCATTCTCAACAA	1-2-2-7-1-1-4	AaaGAtcattctCaACAA	621_4	-18.07	30604
  621	AAAGATCATTCTCAACAA	5-10-3	AAAGAtcattctcaaCAA	621_5	-18.65	30604
  621	AAAGATCATTCTCAACAA	1-1-3-7-3-1-2	AaAGAtcattctCAAcAA	621_6	-18.59	30604
  621	AAAGATCATTCTCAACAA	4-8-2-1-3	AAAGatcattctCAaCAA	621_7	-19.10	30604
  621	AAAGATCATTCTCAACAA	3-1-1-7-2-1-3	AAAgAtcattctCAaCAA	621_8	-18.35	30604
  621	AAAGATCATTCTCAACAA	1-1-2-8-2-1-3	AaAGatcattctCAaCAA	621_9	-18.37	30604
  621	AAAGATCATTCTCAACAA	1-2-2-7-2-1-3	AaaGAtcattctCAaCAA	621_10	-18.74	30604
  621	AAAGATCATTCTCAACAA	5-7-1-2-3	AAAGAtcattctCaaCAA	621_11	-19.32	30604
  622	CAAAGATCATTCTCAACA	1-1-2-8-6	CaAAgatcattcTCAACA	622_1	-20.93	30605
  622	CAAAGATCATTCTCAACA	2-1-1-9-5	CAaAgatcattctCAACA	622_2	-20.68	30605
  622	CAAAGATCATTCTCAACA	1-4-1-7-5	CaaagAtcattctCAACA	622_3	-18.86	30605
  622	CAAAGATCATTCTCAACA	4-1-1-7-1-2-2	CAAAgAtcattctCaaCA	622_4	-19.40	30605
  622	CAAAGATCATTCTCAACA	3-1-2-10-2	CAAaGAtcattctcaaCA	622_5	-19.67	30605
  622	CAAAGATCATTCTCAACA	4-8-2-2-2	CAAAgatcattcTCaaCA	622_6	-20.10	30605
  622	CAAAGATCATTCTCAACA	1-1-2-1-1-7-5	CaAAgAtcattctCAACA	622_7	-20.23	30605
  622	CAAAGATCATTCTCAACA	2-1-1-9-2-1-2	CAaAgatcattctCAaCA	622_8	-19.66	30605
  622	CAAAGATCATTCTCAACA	3-2-1-7-1-1-3	CAAagAtcattctCaACA	622_9	-19.21	30605
  622	CAAAGATCATTCTCAACA	1-3-2-7-1-2-2	CaaaGAtcattctCaaCA	622_10	-18.30	30605
  623	CAAAGATCATTCTCAAC	3-8-6	CAAagatcattCTCAAC	623_1	-19.95	30606
  623	CAAAGATCATTCTCAAC	2-1-1-7-6	CAaAgatcattCTCAAC	623_2	-20.23	30606
  623	CAAAGATCATTCTCAAC	2-2-1-6-6	CAaaGatcattCTCAAC	623_3	-20.15	30606
  623	CAAAGATCATTCTCAAC	1-2-2-6-6	CaaAGatcattCTCAAC	623_4	-20.00	30606
  623	CAAAGATCATTCTCAAC	5-6-1-1-4	CAAAGatcattCtCAAC	623_5	-20.35	30606
  623	CAAAGATCATTCTCAAC	4-7-3-1-2	CAAAgatcattCTCaAC	623_6	-19.28	30606
  623	CAAAGATCATTCTCAAC	3-1-1-6-1-1-4	CAAaGatcattCtCAAC	623_7	-18.81	30606
  623	CAAAGATCATTCTCAAC	2-1-1-7-1-1-4	CAaAgatcattCtCAAC	623_8	-18.36	30606
  623	CAAAGATCATTCTCAAC	1-2-2-6-1-1-4	CaaAGatcattCtCAAC	623_9	-18.12	30606
  623	CAAAGATCATTCTCAAC	4-8-5	CAAAgatcattcTCAAC	623_10	-19.31	30606
  624	CTCAAAGATCATTCTCA	1-2-1-7-6	CtcAaagatcaTTCTCA	624_1	-20.57	30608
  624	CTCAAAGATCATTCTCA	1-1-1-1-1-7-2-1-2	CtCaAagatcatTCtCA	624_2	-18.69	30608
  624	CTCAAAGATCATTCTCA	1-1-2-7-1-2-3	CtCAaagatcaTtcTCA	624_3	-19.51	30608
  624	CTCAAAGATCATTCTCA	3-10-1-1-2	CTCaaagatcattCtCA	624_4	-19.23	30608
  624	CTCAAAGATCATTCTCA	1-1-3-8-4	CtCAAagatcattCTCA	624_5	-21.26	30608
  624	CTCAAAGATCATTCTCA	1-1-3-6-1-1-1-1-2	CtCAAagatcaTtCtCA	624_6	-19.82	30608
  624	CTCAAAGATCATTCTCA	4-7-1-3-2	CTCAaagatcaTtctCA	624_7	-20.18	30608
  624	CTCAAAGATCATTCTCA	1-2-2-7-5	CtcAAagatcatTCTCA	624_8	-20.16	30608
  624	CTCAAAGATCATTCTCA	1-1-2-8-2-1-2	CtCAaagatcatTCtCA	624_9	-19.83	30608
  624	CTCAAAGATCATTCTCA	3-10-4	CTCaaagatcattCTCA	624_10	-21.11	30608
  625	TACACTTAATTATACTTCCA	1-2-1-1-1-7-2-3-2	TacAcTtaattatACttcCA	625_1	-20.33	30666
  625	TACACTTAATTATACTTCCA	1-2-1-2-1-6-1-4-2	TacActTaattatActtcCA	625_2	-19.15	30666
  625	TACACTTAATTATACTTCCA	1-4-1-7-1-1-1-2-2	TacacTtaattatAcTtcCA	625_3	-19.30	30666
  625	TACACTTAATTATACTTCCA	1-1-1-2-2-6-1-4-2	TaCacTTaattatActtcCA	625_4	-20.71	30666
  625	TACACTTAATTATACTTCCA	1-1-1-3-1-8-1-2-2	TaCactTaattatacTtcCA	625_5	-20.00	30666
  625	TACACTTAATTATACTTCCA	1-2-1-1-2-8-1-2-2	TacAcTTaattatacTtcCA	625_6	-20.50	30666
  625	TACACTTAATTATACTTCCA	1-2-1-13-3	TacActtaattatacttCCA	625_7	-20.60	30666
  625	TACACTTAATTATACTTCCA	1-4-1-11-3	TacacTtaattatacttCCA	625_8	-20.96	30666
  625	TACACTTAATTATACTTCCA	2-1-1-1-1-12-2	TAcAcTtaattatacttcCA	625_9	-19.97	30666
  625	TACACTTAATTATACTTCCA	1-1-1-2-1-7-2-3-2	TaCacTtaattatACttcCA	625_10	-20.87	30666
  625	TACACTTAATTATACTTCCA	1-2-1-1-2-6-1-1-1-2-2	TacAcTTaattatAcTtcCA	625_11	-20.69	30666
  625	TACACTTAATTATACTTCCA	1-2-1-1-1-9-1-1-3	TacAcTtaattatacTtCCA	625_12	-21.63	30666
  625	TACACTTAATTATACTTCCA	1-1-1-3-1-10-3	TaCactTaattatacttCCA	625_13	-21.86	30666
  625	TACACTTAATTATACTTCCA	2-1-2-1-1-11-2	TAcACtTaattatacttcCA	625_14	-21.58	30666
  626	TTACACTTAATTATACTTCC	1-3-1-1-1-7-2-2-2	TtacAcTtaattatACttCC	626_1	-19.98	30667
  626	TTACACTTAATTATACTTCC	1-5-1-7-1-1-1-1-2	TtacacTtaattatAcTtCC	626_2	-18.96	30667
  626	TTACACTTAATTATACTTCC	2-4-1-11-2	TTacacTtaattatacttCC	626_3	-19.49	30667
  626	TTACACTTAATTATACTTCC	1-5-1-9-4	TtacacTtaattatacTTCC	626_4	-20.26	30667
  626	TTACACTTAATTATACTTCC	1-1-1-3-1-8-1-2-2	TtAcacTtaattataCttCC	626_5	-19.43	30667
  626	TTACACTTAATTATACTTCC	1-1-2-2-1-7-1-3-2	TtACacTtaattatActtCC	626_6	-19.72	30667
  626	TTACACTTAATTATACTTCC	3-1-1-12-3	TTAcActtaattatactTCC	626_7	-21.33	30667
  626	TTACACTTAATTATACTTCC	1-1-1-1-1-1-1-9-1-1-2	TtAcAcTtaattatacTtCC	626_8	-19.10	30667
  626	TTACACTTAATTATACTTCC	1-2-2-1-1-11-2	TtaCAcTtaattatacttCC	626_9	-20.49	30667
  626	TTACACTTAATTATACTTCC	1-5-1-7-2-1-3	TtacacTtaattatACtTCC	626_10	-20.82	30667
  626	TTACACTTAATTATACTTCC	4-2-1-7-1-3-2	TTACacTtaattatActtCC	626_11	-21.99	30667
  626	TTACACTTAATTATACTTCC	1-1-1-1-3-8-1-2-2	TtAcACTtaattataCttCC	626_12	-21.65	30667
  626	TTACACTTAATTATACTTCC	2-1-2-11-4	TTaCActtaattatacTTCC	626_13	-23.23	30667
  626	TTACACTTAATTATACTTCC	2-2-1-1-1-9-1-1-2	TTacAcTtaattatacTtCC	626_14	-20.15	30667
  627	TTTACACTTAATTATACTTC	2-1-2-8-1-1-5	TTTACacttaattAtACTTC	627_1	-20.02	30668
  627	TTTACACTTAATTATACTTC	2-3-1-7-4-1-2	TTtacActtaattATACtTC	627_2	-19.89	30668
  627	TTTACACTTAATTATACTTC	1-2-1-1-1-7-2-1-4	TttAcActtaattATaCTTC	627_3	-19.35	30668
  627	TTTACACTTAATTATACTTC	1-1-3-8-3-2-2	TtTACacttaattATActTC	627_4	-20.58	30668
  627	TTTACACTTAATTATACTTC	3-2-1-7-3-1-3	TTTacActtaattATAcTTC	627_5	-20.76	30668
  627	TTTACACTTAATTATACTTC	1-3-2-7-2-2-3	TttaCActtaattATacTTC	627_6	-19.58	30668
  627	TTTACACTTAATTATACTTC	3-2-1-7-2-1-4	TTTacActtaattATaCTTC	627_7	-21.21	30668
  627	TTTACACTTAATTATACTTC	3-1-1-8-1-2-4	TTTaCacttaattAtaCTTC	627_8	-20.07	30668
  627	TTTACACTTAATTATACTTC	6-7-1-4-2	TTTACActtaattAtactTC	627_9	-20.56	30668
  627	TTTACACTTAATTATACTTC	4-1-1-7-4-1-2	TTTAcActtaattATACtTC	627_10	-22.36	30668
  627	TTTACACTTAATTATACTTC	3-1-1-1-1-6-3-1-3	TTTaCaCttaattATAcTTC	627_11	-22.29	30668
  627	TTTACACTTAATTATACTTC	2-1-3-7-3-2-2	TTTACActtaattATActTC	627_12	-21.19	30668
  627	TTTACACTTAATTATACTTC	3-1-2-7-2-1-4	TTTaCActtaattATaCTTC	627_13	-23.30	30668
  627	TTTACACTTAATTATACTTC	1-1-4-7-1-2-4	TtTACActtaattAtaCTTC	627_14	-21.94	30668
  628	ATTTACACTTAATTATACTT	2-1-1-2-1-6-3-1-3	ATtTacActtaatTATaCTT	628_1	-21.21	30669
  628	ATTTACACTTAATTATACTT	3-1-1-8-2-1-4	ATTtAcacttaatTAtACTT	628_2	-20.27	30669
  628	ATTTACACTTAATTATACTT	1-1-2-2-1-6-4-1-2	AtTTacActtaatTATAcTT	628_3	-20.33	30669
  628	ATTTACACTTAATTATACTT	1-3-1-1-1-7-6	AtttAcActtaattATACTT	628_4	-19.30	30669
  628	ATTTACACTTAATTATACTT	2-2-2-7-3-2-2	ATttACacttaatTATacTT	628_5	-19.94	30669
  628	ATTTACACTTAATTATACTT	4-1-2-6-2-3-2	ATTTaCActtaatTAtacTT	628_6	-21.29	30669
  628	ATTTACACTTAATTATACTT	1-1-4-7-1-1-1-2-2	AtTTACacttaatTaTacTT	628_7	-19.33	30669
  628	ATTTACACTTAATTATACTT	2-2-3-6-1-2-4	ATttACActtaatTatACTT	628_8	-20.97	30669
  628	ATTTACACTTAATTATACTT	4-2-1-6-1-3-3	ATTTacActtaatTataCTT	628_9	-19.73	30669
  628	ATTTACACTTAATTATACTT	1-1-2-1-2-6-4-1-2	AtTTaCActtaatTATAcTT	628_10	-22.43	30669
  628	ATTTACACTTAATTATACTT	3-2-2-6-2-2-3	ATTtaCActtaatTAtaCTT	628_11	-21.72	30669
  628	ATTTACACTTAATTATACTT	1-2-4-6-2-2-3	AttTACActtaatTAtaCTT	628_12	-22.02	30669
  628	ATTTACACTTAATTATACTT	2-1-1-1-2-6-1-1-5	ATtTaCActtaatTaTACTT	628_13	-23.00	30669
  628	ATTTACACTTAATTATACTT	5-8-1-1-1-1-3	ATTTAcacttaatTaTaCTT	628_14	-21.68	30669
  629	TTCTACTATACTTTCCTCT	1-3-1-7-1-1-1-2-2	TtctActatactTtCctCT	629_1	-21.04	30711
  629	TTCTACTATACTTTCCTCT	1-11-1-1-1-2-2	TtctactatactTtCctCT	629_2	-20.85	30711
  629	TTCTACTATACTTTCCTCT	1-11-1-2-1-1-2	TtctactatactTtcCtCT	629_3	-20.97	30711
  629	TTCTACTATACTTTCCTCT	1-1-1-9-1-4-2	TtCtactatactTtcctCT	629_4	-21.06	30711
  629	TTCTACTATACTTTCCTCT	1-1-1-11-1-2-2	TtCtactatactttCctCT	629_5	-21.53	30711
  629	TTCTACTATACTTTCCTCT	1-3-1-9-1-2-2	TtctActatactttCctCT	629_6	-20.74	30711
  629	TTCTACTATACTTTCCTCT	1-4-1-8-1-2-2	TtctaCtatactttCctCT	629_7	-21.54	30711
  629	TTCTACTATACTTTCCTCT	1-13-1-2-2	TtctactatactttCctCT	629_8	-20.55	30711
  629	TTCTACTATACTTTCCTCT	1-1-1-12-1-1-2	TtCtactatactttcCtCT	629_9	-21.65	30711
  629	TTCTACTATACTTTCCTCT	1-3-1-10-1-1-2	TtctActatactttcCtCT	629_10	-20.86	30711
  629	TTCTACTATACTTTCCTCT	1-14-1-1-2	TtctactatactttcCtCT	629_11	-20.67	30711
  629	TTCTACTATACTTTCCTCT	1-1-1-1-1-7-1-1-1-2-2	TtCtActatactTtCctCT	629_12	-22.02	30711
  629	TTCTACTATACTTTCCTCT	1-1-1-2-1-8-1-2-2	TtCtaCtatactttCctCT	629_13	-22.52	30711
  629	TTCTACTATACTTTCCTCT	1-3-2-8-1-2-2	TtctACtatactttCctCT	629_14	-22.14	30711
  629	TTCTACTATACTTTCCTCT	1-1-1-1-1-10-1-1-2	TtCtActatactttcCtCT	629_15	-21.84	30711
  629	TTCTACTATACTTTCCTCT	1-1-1-2-1-9-1-1-2	TtCtaCtatactttcCtCT	629_16	-22.64	30711
  630	GTTCTACTATACTTTCCTC	1-12-1-1-1-1-2	GttctactatactTtCcTC	630_1	-20.78	30712
  630	GTTCTACTATACTTTCCTC	1-4-1-9-1-1-2	GttctActatactttCcTC	630_2	-20.67	30712
  630	GTTCTACTATACTTTCCTC	1-14-1-1-2	GttctactatactttCcTC	630_3	-20.48	30712
  631	GTTCTACTATACTTTCCT	1-2-1-1-1-7-1-2-2	GttCtActatactTtcCT	631_1	-20.25	30713
  631	GTTCTACTATACTTTCCT	1-2-1-9-1-2-2	GttCtactatactTtcCT	631_2	-20.06	30713
  631	GTTCTACTATACTTTCCT	1-2-1-11-3	GttCtactatactttCCT	631_3	-22.13	30713
  631	GTTCTACTATACTTTCCT	1-4-1-9-3	GttctActatactttCCT	631_4	-21.34	30713
  631	GTTCTACTATACTTTCCT	1-14-3	GttctactatactttCCT	631_5	-21.15	30713
  631	GTTCTACTATACTTTCCT	2-1-1-1-1-10-2	GTtCtActatactttcCT	631_6	-21.50	30713
  631	GTTCTACTATACTTTCCT	2-1-1-12-2	GTtCtactatactttcCT	631_7	-21.30	30713
  631	GTTCTACTATACTTTCCT	1-2-1-1-1-10-2	GttCtActatactttcCT	631_8	-19.95	30713
  631	GTTCTACTATACTTTCCT	1-2-1-12-2	GttCtactatactttcCT	631_9	-19.76	30713
  631	GTTCTACTATACTTTCCT	1-15-2	GttctactatactttcCT	631_10	-18.78	30713
  631	GTTCTACTATACTTTCCT	1-2-1-9-1-1-3	GttCtactatactTtCCT	631_11	-22.43	30713
  631	GTTCTACTATACTTTCCT	2-1-1-1-1-7-1-2-2	GTtCtActatactTtcCT	631_12	-21.80	30713
  631	GTTCTACTATACTTTCCT	1-2-2-8-1-2-2	GttCTactatactTtcCT	631_13	-21.68	30713
  631	GTTCTACTATACTTTCCT	1-2-1-1-1-9-3	GttCtActatactttCCT	631_14	-22.32	30713
  631	GTTCTACTATACTTTCCT	1-2-3-10-2	GttCTActatactttcCT	631_15	-22.60	30713
  632	AGTTCTACTATACTTTCC	1-12-1-2-2	AgttctactatacTttCC	632_1	-19.37	30714
  632	AGTTCTACTATACTTTCC	1-13-1-1-2	AgttctactatactTtCC	632_2	-19.16	30714
  632	AGTTCTACTATACTTTCC	1-1-1-13-2	AgTtctactatactttCC	632_3	-19.51	30714
  632	AGTTCTACTATACTTTCC	1-15-2	AgttctactatactttCC	632_4	-18.86	30714
  632	AGTTCTACTATACTTTCC	1-1-1-10-1-2-2	AgTtctactatacTttCC	632_5	-20.03	30714
  632	AGTTCTACTATACTTTCC	1-4-1-7-1-2-2	AgttcTactatacTttCC	632_6	-20.31	30714
  632	AGTTCTACTATACTTTCC	2-14-2	AGttctactatactttCC	632_7	-20.26	30714
  632	AGTTCTACTATACTTTCC	1-2-1-12-2	AgtTctactatactttCC	632_8	-19.23	30714
  632	AGTTCTACTATACTTTCC	1-4-1-10-2	AgttcTactatactttCC	632_9	-19.80	30714
  632	AGTTCTACTATACTTTCC	2-10-1-3-2	AGttctactataCtttCC	632_10	-21.25	30714
  632	AGTTCTACTATACTTTCC	1-4-1-6-1-3-2	AgttcTactataCtttCC	632_11	-20.79	30714
  632	AGTTCTACTATACTTTCC	1-4-1-7-2-1-2	AgttcTactatacTTtCC	632_12	-21.13	30714
  632	AGTTCTACTATACTTTCC	1-1-1-11-1-1-2	AgTtctactatactTtCC	632_13	-19.82	30714
  632	AGTTCTACTATACTTTCC	1-3-1-11-2	AgttCtactatactttCC	632_14	-19.83	30714
  633	CAACATTATTAACCACCTTA	1-13-3-1-2	CaacattattaaccACCtTA	633_1	-22.44	33376
  633	CAACATTATTAACCACCTTA	4-10-1-2-3	CAACattattaaccAccTTA	633_2	-22.98	33376
  633	CAACATTATTAACCACCTTA	2-2-1-10-1-1-3	CAacAttattaaccaCcTTA	633_3	-21.97	33376
  633	CAACATTATTAACCACCTTA	1-4-2-8-1-2-2	CaacaTTattaaccaCctTA	633_4	-21.08	33376
  633	CAACATTATTAACCACCTTA	1-1-2-11-1-2-2	CaACattattaaccaCctTA	633_5	-20.90	33376
  633	CAACATTATTAACCACCTTA	1-2-2-13-2	CaaCAttattaaccacctTA	633_6	-20.76	33376
  633	CAACATTATTAACCACCTTA	1-1-1-1-1-11-1-1-2	CaAcAttattaaccacCtTA	633_7	-19.97	33376
  633	CAACATTATTAACCACCTTA	1-15-4	CaacattattaaccacCTTA	633_8	-21.21	33376
  633	CAACATTATTAACCACCTTA	2-4-1-11-2	CAacatTattaaccacctTA	633_9	-20.83	33376
  634	CAACATTATTAACCACCTT	2-10-2-3-2	CAacattattaaCCaccTT	634_1	-21.86	33377
  634	CAACATTATTAACCACCTT	1-14-4	CaacattattaaccaCCTT	634_2	-21.36	33377
  634	CAACATTATTAACCACCTT	1-1-1-11-1-1-3	CaAcattattaaccAcCTT	634_3	-19.54	33377
  634	CAACATTATTAACCACCTT	3-1-1-11-3	CAAcAttattaaccacCTT	634_4	-21.13	33377
  634	CAACATTATTAACCACCTT	3-11-2-1-2	CAAcattattaaccACcTT	634_5	-20.84	33377
  634	CAACATTATTAACCACCTT	2-1-2-9-1-1-3	CAaCAttattaaccAcCTT	634_6	-22.76	33377
  634	CAACATTATTAACCACCTT	2-1-2-10-1-1-2	CAaCAttattaaccaCcTT	634_7	-21.83	33377
  634	CAACATTATTAACCACCTT	1-1-2-11-1-1-2	CaACattattaaccaCcTT	634_8	-19.70	33377
  634	CAACATTATTAACCACCTT	1-2-1-12-3	CaaCattattaaccacCTT	634_9	-19.66	33377
  635	GCAACATTATTAACCACCT	1-1-1-2-1-6-2-3-2	GcAacAttattaACcacCT	635_1	-21.56	33378
  635	GCAACATTATTAACCACCT	1-1-2-1-1-6-1-2-1-1-2	GcAAcAttattaAccAcCT	635_2	-21.14	33378
  635	GCAACATTATTAACCACCT	1-11-2-1-1-1-2	GcaacattattaACcAcCT	635_3	-21.59	33378
  635	GCAACATTATTAACCACCT	1-4-1-6-1-3-3	GcaacAttattaAccaCCT	635_4	-22.69	33378
  635	GCAACATTATTAACCACCT	1-1-1-1-1-7-1-4-2	GcAaCattattaAccacCT	635_5	-21.01	33378
  635	GCAACATTATTAACCACCT	1-11-1-1-1-2-2	GcaacattattaAcCacCT	635_6	-20.83	33378
  635	GCAACATTATTAACCACCT	2-3-1-6-1-4-2	GCaacAttattaAccacCT	635_7	-22.63	33378
  635	GCAACATTATTAACCACCT	1-1-1-12-1-1-2	GcAacattattaaccAcCT	635_8	-20.05	33378
  635	GCAACATTATTAACCACCT	1-2-1-1-1-11-2	GcaAcAttattaaccacCT	635_9	-20.30	33378
  636	AGCAACATTATTAACCACC	1-2-1-9-2-1-3	AgcAacattattaACcACC	636_1	-22.13	33379
  636	AGCAACATTATTAACCACC	1-11-1-1-1-2-2	AgcaacattattAaCcaCC	636_2	-20.80	33379
  636	AGCAACATTATTAACCACC	1-4-1-6-2-3-2	AgcaaCattattAAccaCC	636_3	-21.32	33379
  636	AGCAACATTATTAACCACC	1-2-2-7-1-2-1-1-2	AgcAAcattattAacCaCC	636_4	-21.29	33379
  636	AGCAACATTATTAACCACC	2-11-1-3-2	AGcaacattattaAccaCC	636_5	-21.75	33379
  636	AGCAACATTATTAACCACC	1-1-1-1-1-8-1-2-3	AgCaAcattattaAccACC	636_6	-22.16	33379
  636	AGCAACATTATTAACCACC	1-2-1-1-1-6-1-3-3	AgcAaCattattAaccACC	636_7	-21.33	33379
  636	AGCAACATTATTAACCACC	2-1-2-12-2	AGcAAcattattaaccaCC	636_8	-22.02	33379
  636	AGCAACATTATTAACCACC	1-15-3	AgcaacattattaaccACC	636_9	-20.45	33379
  637	AGCAACATTATTAACCAC	2-1-1-9-5	AGcAacattattaACCAC	637_1	-21.97	33380
  637	AGCAACATTATTAACCAC	1-3-1-7-6	AgcaAcattattAACCAC	637_2	-21.20	33380
  637	AGCAACATTATTAACCAC	2-10-2-1-3	AGcaacattattAAcCAC	637_3	-19.42	33380
  637	AGCAACATTATTAACCAC	1-2-1-8-1-1-4	AgcAacattattAaCCAC	637_4	-19.84	33380
  637	AGCAACATTATTAACCAC	3-9-3-1-2	AGCaacattattAACcAC	637_5	-20.94	33380
  637	AGCAACATTATTAACCAC	1-1-3-7-3-1-2	AgCAAcattattAACcAC	637_6	-20.15	33380
  637	AGCAACATTATTAACCAC	1-1-3-7-2-1-3	AgCAAcattattAAcCAC	637_7	-20.96	33380
  637	AGCAACATTATTAACCAC	5-7-1-3-2	AGCAAcattattAaccAC	637_8	-21.24	33380
  637	AGCAACATTATTAACCAC	3-1-1-8-1-2-2	AGCaAcattattaAccAC	637_9	-19.86	33380
  638	GTTTCCATCTACTATTAAT	1-3-1-7-1-1-1-1-3	GtttCcatctacTaTtAAT	638_1	-19.59	39806
  638	GTTTCCATCTACTATTAAT	1-1-1-9-2-3-2	GtTtccatctacTAttaAT	638_2	-19.50	39806
  638	GTTTCCATCTACTATTAAT	1-4-1-6-2-2-3	GtttcCatctacTAttAAT	638_3	-20.09	39806
  638	GTTTCCATCTACTATTAAT	1-3-1-8-1-2-3	GtttCcatctactAttAAT	638_4	-18.30	39806
  638	GTTTCCATCTACTATTAAT	3-1-1-8-1-3-2	GTTtCcatctactAttaAT	638_5	-20.35	39806
  638	GTTTCCATCTACTATTAAT	1-2-2-12-2	GttTCcatctactattaAT	638_6	-18.88	39806
  638	GTTTCCATCTACTATTAAT	1-1-1-11-1-1-3	GtTtccatctactaTtAAT	638_7	-18.18	39806
  638	GTTTCCATCTACTATTAAT	2-2-1-10-1-1-2	GTttCcatctactatTaAT	638_8	-20.16	39806
  638	GTTTCCATCTACTATTAAT	1-1-1-1-2-10-3	GtTtCCatctactattAAT	638_9	-20.69	39806
  638	GTTTCCATCTACTATTAAT	2-2-1-7-1-3-3	GTttCcatctacTattAAT	638_10	-20.69	39806
  638	GTTTCCATCTACTATTAAT	1-1-1-10-2-1-3	GtTtccatctactATTAAT	638_11	-19.08	39806
  638	GTTTCCATCTACTATTAAT	1-3-1-8-1-1-1-1-2	GtttCcatctactAtTaAT	638_12	-18.72	39806
  638	GTTTCCATCTACTATTAAT	1-2-3-7-1-2-3	GttTCCatctactAttAAT	638_13	-21.47	39806
  638	GTTTCCATCTACTATTAAT	1-1-1-1-2-11-2	GtTtCCatctactattaAT	638_14	-20.37	39806
  639	GTTTCCATCTACTATTAA	1-11-2-1-3	GtttccatctacTAtTAA	639_1	-19.21	39807
  639	GTTTCCATCTACTATTAA	1-3-1-7-1-1-4	GtttCcatctacTaTTAA	639_2	-19.80	39807
  639	GTTTCCATCTACTATTAA	3-1-1-7-2-2-2	GTTtCcatctacTAttAA	639_3	-20.57	39807
  639	GTTTCCATCTACTATTAA	2-2-1-7-1-1-1-1-2	GTttCcatctacTaTtAA	639_4	-19.07	39807
  639	GTTTCCATCTACTATTAA	1-3-2-7-2-1-2	GtttCCatctactATTAA	639_5	-19.67	39807
  639	GTTTCCATCTACTATTAA	3-2-1-6-1-3-2	GTTtcCatctacTattAA	639_6	-19.25	39807
  639	GTTTCCATCTACTATTAA	1-1-3-8-1-2-2	GtTTCcatctactAttAA	639_7	-18.04	39807
  639	GTTTCCATCTACTATTAA	1-1-1-1-2-10-2	GtTtCCatctactattAA	639_8	-18.62	39807
  639	GTTTCCATCTACTATTAA	3-1-1-9-4	GTTtCcatctactaTTAA	639_9	-21.21	39807
  639	GTTTCCATCTACTATTAA	1-3-2-6-2-2-2	GtttCCatctacTAttAA	639_10	-20.39	39807
  639	GTTTCCATCTACTATTAA	1-1-3-7-1-1-1-1-2	GtTTCcatctacTaTtAA	639_11	-19.32	39807
  639	GTTTCCATCTACTATTAA	2-2-1-7-1-2-3	GTttCcatctacTatTAA	639_12	-20.39	39807
  639	GTTTCCATCTACTATTAA	2-2-1-8-2-1-2	GTttCcatctactATTAA	639_13	-19.03	39807
  639	GTTTCCATCTACTATTAA	1-1-1-1-2-8-4	GtTtCCatctactaTTAA	639_14	-21.34	39807
  640	TGTTTCCATCTACTATTA	1-1-1-11-1-1-2	TgTttccatctactAtTA	640_1	-18.41	39808
  640	TGTTTCCATCTACTATTA	1-2-1-9-2-1-2	TgtTtccatctacTAtTA	640_2	-20.03	39808
  640	TGTTTCCATCTACTATTA	1-4-1-7-1-2-2	TgtttCcatctacTatTA	640_3	-19.37	39808
  640	TGTTTCCATCTACTATTA	1-4-1-8-4	TgtttCcatctactATTA	640_4	-20.28	39808
  640	TGTTTCCATCTACTATTA	1-4-1-8-1-1-2	TgtttCcatctactAtTA	640_5	-18.52	39808
  640	TGTTTCCATCTACTATTA	1-1-2-1-1-10-2	TgTTtCcatctactatTA	640_6	-19.89	39808
  640	TGTTTCCATCTACTATTA	1-4-1-9-3	TgtttCcatctactaTTA	640_7	-19.37	39808
  640	TGTTTCCATCTACTATTA	1-2-1-1-1-10-2	TgtTtCcatctactatTA	640_8	-18.73	39808
  640	TGTTTCCATCTACTATTA	1-4-1-10-2	TgtttCcatctactatTA	640_9	-18.42	39808
  640	TGTTTCCATCTACTATTA	1-4-1-6-1-1-4	TgtttCcatctaCtATTA	640_10	-21.27	39808
  640	TGTTTCCATCTACTATTA	2-1-1-9-2-1-2	TGtTtccatctacTAtTA	640_11	-21.24	39808
  640	TGTTTCCATCTACTATTA	1-3-2-8-1-1-2	TgttTCcatctactAtTA	640_12	-19.51	39808
  640	TGTTTCCATCTACTATTA	2-1-1-1-1-10-2	TGtTtCcatctactatTA	640_13	-19.94	39808
  640	TGTTTCCATCTACTATTA	1-1-1-2-1-10-2	TgTttCcatctactatTA	640_14	-19.08	39808
  641	ACTCTGCAATACACCAA	2-1-1-8-2-1-2	ACtCtgcaatacACcAA	641_1	-19.61	44439
  641	ACTCTGCAATACACCAA	2-2-1-6-1-1-1-1-2	ACtcTgcaataCaCcAA	641_2	-19.77	44439
  641	ACTCTGCAATACACCAA	1-2-1-7-1-1-1-1-2	ActCtgcaataCaCcAA	641_3	-18.35	44439
  641	ACTCTGCAATACACCAA	2-1-2-6-2-2-2	ACtCTgcaataCAccAA	641_4	-22.21	44439
  641	ACTCTGCAATACACCAA	1-3-1-7-1-1-3	ActcTgcaatacAcCAA	641_5	-19.05	44439
  641	ACTCTGCAATACACCAA	4-8-1-2-2	ACTCtgcaatacAccAA	641_6	-20.30	44439
  641	ACTCTGCAATACACCAA	2-1-2-9-3	ACtCTgcaatacacCAA	641_7	-21.96	44439
  641	ACTCTGCAATACACCAA	2-11-4	ACtctgcaatacaCCAA	641_8	-21.68	44439
  641	ACTCTGCAATACACCAA	1-1-2-10-3	AcTCtgcaatacacCAA	641_9	-20.07	44439
  642	CTGTATACACCATCCCA	1-10-1-1-1-1-2	CtgtatacaccAtCcCA	642_1	-21.99	46391
  642	CTGTATACACCATCCCA	1-10-1-3-2	CtgtatacaccAtccCA	642_2	-21.22	46391
  642	CTGTATACACCATCCCA	1-1-1-8-1-3-2	CtGtatacaccAtccCA	642_3	-21.53	46391
  642	CTGTATACACCATCCCA	1-2-1-7-1-3-2	CtgTatacaccAtccCA	642_4	-22.31	46391
  642	CTGTATACACCATCCCA	1-3-1-6-1-3-2	CtgtAtacaccAtccCA	642_5	-21.32	46391
  642	CTGTATACACCATCCCA	1-11-2-1-2	CtgtatacaccaTCcCA	642_6	-23.06	46391
  642	CTGTATACACCATCCCA	1-1-1-1-1-8-1-1-2	CtGtAtacaccatCcCA	642_7	-22.35	46391
  642	CTGTATACACCATCCCA	1-1-1-10-1-1-2	CtGtatacaccatCcCA	642_8	-22.25	46391
  642	CTGTATACACCATCCCA	1-2-1-9-1-1-2	CtgTatacaccatCcCA	642_9	-23.02	46391
  642	CTGTATACACCATCCCA	1-3-1-8-1-1-2	CtgtAtacaccatCcCA	642_10	-22.04	46391
  642	CTGTATACACCATCCCA	1-12-1-1-2	CtgtatacaccatCcCA	642_11	-21.94	46391
  642	CTGTATACACCATCCCA	2-2-1-10-2	CTgtAtacaccatccCA	642_12	-22.95	46391
  642	CTGTATACACCATCCCA	1-1-1-1-1-10-2	CtGtAtacaccatccCA	642_13	-21.58	46391
  642	CTGTATACACCATCCCA	1-1-1-12-2	CtGtatacaccatccCA	642_14	-21.48	46391
  642	CTGTATACACCATCCCA	1-2-2-10-2	CtgTAtacaccatccCA	642_15	-23.39	46391
  642	CTGTATACACCATCCCA	1-3-1-10-2	CtgtAtacaccatccCA	642_16	-21.27	46391
  642	CTGTATACACCATCCCA	1-14-2	CtgtatacaccatccCA	642_17	-21.17	46391
  642	CTGTATACACCATCCCA	1-3-1-6-3-1-2	CtgtAtacaccATCcCA	642_18	-24.02	46391
  642	CTGTATACACCATCCCA	1-1-1-8-1-1-1-1-2	CtGtatacaccAtCcCA	642_19	-22.30	46391
  642	CTGTATACACCATCCCA	1-1-3-6-1-3-2	CtGTAtacaccAtccCA	642_20	-24.64	46391
  642	CTGTATACACCATCCCA	2-2-1-8-1-1-2	CTgtAtacaccatCcCA	642_21	-23.72	46391
  642	CTGTATACACCATCCCA	1-3-1-9-3	CtgtAtacaccatcCCA	642_22	-23.55	46391
  643	TCTGTATACACCATCCCA	1-4-1-8-1-1-2	TctgtAtacaccatCcCA	643_1	-22.94	46391
  644	TCTGTATACACCATCCC	2-10-1-2-2	TCtgtatacaccAtcCC	644_1	-22.70	46392
  644	TCTGTATACACCATCCC	1-11-1-2-2	TctgtatacaccAtcCC	644_2	-21.11	46392
  644	TCTGTATACACCATCCC	2-1-1-11-2	TCtGtatacaccatcCC	644_3	-22.96	46392
  644	TCTGTATACACCATCCC	2-13-2	TCtgtatacaccatcCC	644_4	-22.65	46392
  644	TCTGTATACACCATCCC	3-9-1-2-2	TCTgtatacaccAtcCC	644_5	-24.39	46392
  644	TCTGTATACACCATCCC	2-1-1-8-1-2-2	TCtGtatacaccAtcCC	644_6	-23.01	46392
  645	TTCTGTATACACCATCCC	1-11-1-3-2	TtctgtatacacCatcCC	645_1	-22.57	46392
  645	TTCTGTATACACCATCCC	1-1-1-10-1-2-2	TtCtgtatacaccAtcCC	645_2	-23.02	46392
  645	TTCTGTATACACCATCCC	1-3-1-8-1-2-2	TtctGtatacaccAtcCC	645_3	-22.36	46392
  645	TTCTGTATACACCATCCC	1-12-1-2-2	TtctgtatacaccAtcCC	645_4	-22.05	46392
  645	TTCTGTATACACCATCCC	1-15-2	TtctgtatacaccatcCC	645_5	-22.00	46392
  645	TTCTGTATACACCATCCC	1-4-1-6-2-2-2	TtctgTatacacCAtcCC	645_6	-25.12	46392
  645	TTCTGTATACACCATCCC	1-3-1-8-1-1-3	TtctGtatacaccAtCCC	645_7	-24.73	46392
  645	TTCTGTATACACCATCCC	3-10-1-2-2	TTCtgtatacaccAtcCC	645_8	-24.52	46392
  645	TTCTGTATACACCATCCC	1-1-2-9-1-2-2	TtCTgtatacaccAtcCC	645_9	-24.71	46392
  645	TTCTGTATACACCATCCC	1-1-1-1-1-8-1-2-2	TtCtGtatacaccAtcCC	645_10	-23.34	46392
  646	TTCTGTATACACCATCC	1-10-1-3-2	TtctgtatacaCcatCC	646_1	-19.96	46393
  646	TTCTGTATACACCATCC	1-12-4	TtctgtatacaccATCC	646_2	-21.16	46393
  646	TTCTGTATACACCATCC	2-11-1-1-2	TTctgtatacaccAtCC	646_3	-20.11	46393
  646	TTCTGTATACACCATCC	1-2-1-9-1-1-2	TtcTgtatacaccAtCC	646_4	-20.24	46393
  646	TTCTGTATACACCATCC	1-3-1-8-1-1-2	TtctGtatacaccAtCC	646_5	-19.54	46393
  646	TTCTGTATACACCATCC	1-2-1-8-1-2-2	TtcTgtatacacCatCC	646_6	-20.77	46393
  646	TTCTGTATACACCATCC	1-12-1-1-2	TtctgtatacaccAtCC	646_7	-19.23	46393
  646	TTCTGTATACACCATCC	1-3-1-7-1-1-3	TtctGtatacacCaTCC	646_8	-21.19	46393
  646	TTCTGTATACACCATCC	1-1-1-1-1-10-2	TtCtGtatacaccatCC	646_9	-20.47	46393
  646	TTCTGTATACACCATCC	1-1-1-12-2	TtCtgtatacaccatCC	646_10	-20.16	46393
  646	TTCTGTATACACCATCC	1-1-1-11-3	TtCtgtatacaccaTCC	646_11	-21.28	46393
  646	TTCTGTATACACCATCC	1-3-1-9-3	TtctGtatacaccaTCC	646_12	-20.61	46393
  646	TTCTGTATACACCATCC	1-13-3	TtctgtatacaccaTCC	646_13	-20.30	46393
  646	TTCTGTATACACCATCC	3-1-1-10-2	TTCtGtatacaccatCC	646_14	-21.96	46393
  646	TTCTGTATACACCATCC	3-12-2	TTCtgtatacaccatCC	646_15	-21.65	46393
  646	TTCTGTATACACCATCC	1-1-2-11-2	TtCTgtatacaccatCC	646_16	-21.84	46393
  646	TTCTGTATACACCATCC	1-2-1-11-2	TtcTgtatacaccatCC	646_17	-20.19	46393
  646	TTCTGTATACACCATCC	1-3-1-10-2	TtctGtatacaccatCC	646_18	-19.49	46393
  646	TTCTGTATACACCATCC	1-14-2	TtctgtatacaccatCC	646_19	-19.18	46393
  646	TTCTGTATACACCATCC	3-8-1-3-2	TTCtgtatacaCcatCC	646_20	-22.44	46393
  646	TTCTGTATACACCATCC	1-3-1-6-1-3-2	TtctGtatacaCcatCC	646_21	-20.27	46393
  646	TTCTGTATACACCATCC	1-3-1-7-2-1-2	TtctGtatacacCAtCC	646_22	-21.53	46393
  646	TTCTGTATACACCATCC	1-1-1-9-1-2-2	TtCtgtatacacCatCC	646_23	-20.74	46393
  646	TTCTGTATACACCATCC	1-1-1-10-1-1-2	TtCtgtatacaccAtCC	646_24	-20.21	46393
  647	AGCTTTTAACCAGAGT	2-10-4	AGcttttaaccaGAGT	647_1	-21.73	EX-EX
  648	AGCTTTTAACCAGAGTG	2-11-4	AGcttttaaccagAGTG	648_1	-22.27	EX-EX
  649	AGCTTTTAACCAGAGTGG	1-14-3	AgcttttaaccagagTGG	649_1	-21.63	EX-EX
  650	AGCTTTTAACCAGAGTGGC	1-16-2	AgcttttaaccagagtgGC	650_1	-23.20	EX-EX
  651	AGCTTTTAACCAGAGTGGCA	1-17-2	AgcttttaaccagagtggCA	651_1	-24.11	EX-EX
  652	CAGCTTTTAACCAGAGT	2-12-3	CAgcttttaaccagAGT	652_1	-21.65	EX-EX
  653	CAGCTTTTAACCAGAGTG	3-13-2	CAGcttttaaccagagTG	653_1	-22.27	EX-EX
  654	CAGCTTTTAACCAGAGTGG	1-15-3	CagcttttaaccagagTGG	654_1	-22.97	EX-EX
  655	CAGCTTTTAACCAGAGTGGC	1-17-2	CagcttttaaccagagtgGC	655_1	-24.53	EX-EX
  656	CTTTTAACCAGAGTG	4-7-4	CTTTtaaccagAGTG	656_1	-20.12	EX-EX
  657	CTTTTAACCAGAGTGG	4-9-3	CTTTtaaccagagTGG	657_1	-20.92	EX-EX
  658	CTTTTAACCAGAGTGGC	4-11-2	CTTTtaaccagagtgGC	658_1	-22.48	EX-EX
  659	CTTTTAACCAGAGTGGCA	1-14-3	CttttaaccagagtgGCA	659_1	-22.96	EX-EX
  660	CTTTTAACCAGAGTGGCAT	3-13-3	CTTttaaccagagtggCAT	660_1	-24.65	EX-EX
  661	CTTTTAACCAGAGTGGCATC	2-16-2	CTtttaaccagagtggcaTC	661_1	-23.19	EX-EX
  662	GCTTTTAACCAGAGT	3-9-3	GCTtttaaccagAGT	662_1	-21.02	EX-EX
  663	GCTTTTAACCAGAGTG	4-10-2	GCTTttaaccagagTG	663_1	-21.02	EX-EX
  664	GCTTTTAACCAGAGTGG	1-12-4	GcttttaaccagaGTGG	664_1	-22.24	EX-EX
  665	GCTTTTAACCAGAGTGGC	1-14-3	GcttttaaccagagtGGC	665_1	-23.42	EX-EX
  666	GCTTTTAACCAGAGTGGCA	1-16-2	GcttttaaccagagtggCA	666_1	-22.94	EX-EX
  667	GCTTTTAACCAGAGTGGCAT	1-16-3	GcttttaaccagagtggCAT	667_1	-25.01	EX-EX
  668	TCAGCTTTTAACCAGAGT	2-13-3	TCagcttttaaccagAGT	668_1	-22.18	EX-EX
  669	TCAGCTTTTAACCAGAGTG	2-14-3	TCagcttttaaccagaGTG	669_1	-23.15	EX-EX
  670	TCAGCTTTTAACCAGAGTGG	2-16-2	TCagcttttaaccagagtGG	670_1	-23.41	EX-EX
  671	TTCAGCTTTTAACCAGAGT	2-14-3	TTcagcttttaaccagAGT	671_1	-22.72	EX-EX
  672	TTCAGCTTTTAACCAGAGTG	2-15-3	TTcagcttttaaccagaGTG	672_1	-23.69	EX-EX
  673	TTTCAGCTTTTAACCAGAGT	2-15-3	TTtcagcttttaaccagAGT	673_1	-23.66	EX-EX
  674	TTTTAACCAGAGTGGC	1-11-4	TtttaaccagagTGGC	674_1	-20.81	EX-EX
  675	TTTTAACCAGAGTGGCA	3-11-3	TTTtaaccagagtgGCA	675_1	-22.30	EX-EX
  676	TTTTAACCAGAGTGGCAT	4-11-3	TTTTaaccagagtggCAT	676_1	-23.21	EX-EX
  677	TTTTAACCAGAGTGGCATC	4-13-2	TTTTaaccagagtggcaTC	677_1	-22.57	EX-EX
  678	TTTTAACCAGAGTGGCATCC	2-16-2	TTttaaccagagtggcatCC	678_1	-24.58	EX-EX
  679	ATCAATATCTTCTCACT	1-1-2-7-1-1-1-1-2	AtCAatatcttCtCaCT	679_1	-19.16	5782
  679	ATCAATATCTTCTCACT	5-6-1-2-3	ATCAAtatcttCtcACT	679_2	-21.49	5782
  679	ATCAATATCTTCTCACT	1-1-1-1-1-7-5	AtCaAtatcttcTCACT	679_3	-20.18	5782
  679	ATCAATATCTTCTCACT	1-1-3-8-4	AtCAAtatcttctCACT	679_4	-20.66	5782
  679	ATCAATATCTTCTCACT	3-10-1-1-2	ATCaatatcttctCaCT	679_5	-18.62	5782
  680	TATCAATATCTTCTCACT	2-2-1-7-1-1-1-1-2	TAtcAatatcttCtCaCT	680_1	-19.31	5782
  680	TATCAATATCTTCTCACT	1-1-2-8-1-1-1-1-2	TaTCaatatcttCtCaCT	680_2	-19.89	5782
  680	TATCAATATCTTCTCACT	1-2-3-6-1-2-3	TatCAAtatcttCtcACT	680_3	-20.66	5782
  680	TATCAATATCTTCTCACT	1-2-3-7-2-1-2	TatCAAtatcttcTCaCT	680_4	-20.99	5782
  680	TATCAATATCTTCTCACT	2-1-1-10-4	TAtCaatatcttctCACT	680_5	-20.89	5782
  681	TATCAATATCTTCTCAC	4-7-2-1-3	TATCaatatctTCtCAC	681_1	-21.30	5783
  681	TATCAATATCTTCTCAC	1-2-2-6-2-1-3	TatCAatatctTCtCAC	681_2	-19.73	5783
  681	TATCAATATCTTCTCAC	2-1-1-8-5	TAtCaatatcttCTCAC	681_3	-20.26	5783
  681	TATCAATATCTTCTCAC	1-1-3-7-5	TaTCAatatcttCTCAC	681_4	-21.74	5783
  681	TATCAATATCTTCTCAC	5-9-3	TATCAatatcttctCAC	681_5	-20.83	5783
  682	TTATCAATATCTTCTCAC	1-1-1-1-2-6-2-2-2	TtAtCAatatctTCtcAC	682_1	-18.32	5783
  682	TTATCAATATCTTCTCAC	1-3-1-8-5	TtatCaatatcttCTCAC	682_2	-19.71	5783
  682	TTATCAATATCTTCTCAC	3-10-1-1-3	TTAtcaatatcttCtCAC	682_3	-19.53	5783
  682	TTATCAATATCTTCTCAC	2-1-2-8-1-1-3	TTaTCaatatcttCtCAC	682_4	-20.20	5783
  682	TTATCAATATCTTCTCAC	1-2-3-9-3	TtaTCAatatcttctCAC	682_5	-19.47	5783
  683	TTATCAATATCTTCTCACT	1-1-1-1-1-8-1-1-1-1-2	TtAtCaatatcttCtCaCT	683_1	-19.45	5782
  683	TTATCAATATCTTCTCACT	1-3-1-8-1-1-1-1-2	TtatCaatatcttCtCaCT	683_2	-19.35	5782
  683	TTATCAATATCTTCTCACT	1-1-1-1-1-8-1-2-3	TtAtCaatatcttCtcACT	683_3	-19.33	5782
  683	TTATCAATATCTTCTCACT	1-1-1-2-1-7-1-3-2	TtAtcAatatcttCtcaCT	683_4	-18.18	5782
  683	TTATCAATATCTTCTCACT	1-1-1-2-1-9-4	TtAtcAatatcttctCACT	683_5	-19.84	5782
  684	ACCTTTCTTTAACCCTTT	2-1-1-8-2-1-3	ACcTttctttaaCCcTTT	684_1	-25.24	8113
  684	ACCTTTCTTTAACCCTTT	2-10-1-1-1-1-2	ACctttctttaaCcCtTT	684_2	-22.31	8113
  684	ACCTTTCTTTAACCCTTT	1-1-1-9-1-1-1-1-2	AcCtttctttaaCcCtTT	684_3	-22.01	8113
  684	ACCTTTCTTTAACCCTTT	1-1-1-1-1-9-1-1-2	AcCtTtctttaaccCtTT	684_4	-21.53	8113
  684	ACCTTTCTTTAACCCTTT	1-1-1-11-1-1-2	AcCtttctttaaccCtTT	684_5	-21.23	8113
  685	TACCTTTCTTTAACCCTTT	1-2-1-8-1-1-1-2-2	TacCtttctttaAcCctTT	685_1	-22.44	8113
  685	TACCTTTCTTTAACCCTTT	1-2-1-1-1-7-1-1-1-1-2	TacCtTtctttaaCcCtTT	685_2	-23.32	8113
  685	TACCTTTCTTTAACCCTTT	2-1-1-10-1-1-3	TAcCtttctttaacCcTTT	685_3	-24.28	8113
  685	TACCTTTCTTTAACCCTTT	1-1-1-12-1-1-2	TaCctttctttaaccCtTT	685_4	-22.13	8113
  685	TACCTTTCTTTAACCCTTT	1-2-1-11-1-1-2	TacCtttctttaaccCtTT	685_5	-22.23	8113
  686	ATACCTTTCTTTAACCC	1-2-1-7-1-1-1-1-2	AtaCctttcttTaAcCC	686_1	-20.53	8116
  686	ATACCTTTCTTTAACCC	1-3-1-6-1-3-2	AtacCtttcttTaacCC	686_2	-20.21	8116
  686	ATACCTTTCTTTAACCC	2-2-1-7-2-1-2	ATacCtttctttAAcCC	686_3	-21.89	8116
  686	ATACCTTTCTTTAACCC	1-1-1-1-1-8-1-1-2	AtAcCtttctttaAcCC	686_4	-20.10	8116
  686	ATACCTTTCTTTAACCC	1-2-1-10-3	AtaCctttctttaaCCC	686_5	-21.76	8116
  687	ATACCTTTCTTTAACCCTT	1-3-2-6-1-2-4	AtacCTttctttAacCCTT	687_1	-26.10	8114
  687	ATACCTTTCTTTAACCCTT	1-1-1-1-1-8-1-1-1-1-2	AtAcCtttctttaAcCcTT	687_2	-22.23	8114
  687	ATACCTTTCTTTAACCCTT	1-2-1-9-1-1-1-1-2	AtaCctttctttaAcCcTT	687_3	-21.93	8114
  687	ATACCTTTCTTTAACCCTT	1-2-1-1-1-8-2-1-2	AtaCcTttctttaaCCcTT	687_4	-24.41	8114
  687	ATACCTTTCTTTAACCCTT	1-3-1-11-3	AtacCtttctttaaccCTT	687_5	-22.51	8114
  688	ATACCTTTCTTTAACCCTTT	1-3-1-8-1-1-1-2-2	AtacCtttctttaAcCctTT	688_1	-22.83	8113
  688	ATACCTTTCTTTAACCCTTT	1-3-1-9-1-1-1-1-2	AtacCtttctttaaCcCtTT	688_2	-23.41	8113
  688	ATACCTTTCTTTAACCCTTT	1-4-2-7-1-2-3	AtaccTTtctttaaCccTTT	688_3	-23.98	8113
  688	ATACCTTTCTTTAACCCTTT	1-1-1-1-1-10-1-1-3	AtAcCtttctttaacCcTTT	688_4	-23.63	8113
  688	ATACCTTTCTTTAACCCTTT	1-2-1-12-1-1-2	AtaCctttctttaaccCtTT	688_5	-22.52	8113
  689	ATACCTTTCTTTAACCCT	1-3-2-6-2-2-2	AtacCTttctttAAccCT	689_1	-22.61	8115
  689	ATACCTTTCTTTAACCCT	1-1-1-1-2-8-1-1-2	AtAcCTttctttaaCcCT	689_2	-22.85	8115
  689	ATACCTTTCTTTAACCCT	1-2-1-10-1-1-2	AtaCctttctttaaCcCT	689_3	-21.36	8115
  689	ATACCTTTCTTTAACCCT	1-2-3-10-2	AtaCCTttctttaaccCT	689_4	-24.26	8115
  689	ATACCTTTCTTTAACCCT	1-3-1-11-2	AtacCtttctttaaccCT	689_5	-20.69	8115
  690	TATACCTTTCTTTAACCCT	2-2-1-10-1-1-2	TAtaCctttctttaaCcCT	690_1	-23.60	8115
  690	TATACCTTTCTTTAACCCT	1-4-1-9-1-1-2	TatacCtttctttaaCcCT	690_2	-22.57	8115
  690	TATACCTTTCTTTAACCCT	2-3-1-11-2	TAtacCtttctttaaccCT	690_3	-22.92	8115
  690	TATACCTTTCTTTAACCCT	1-3-1-12-2	TataCctttctttaaccCT	690_4	-21.68	8115
  690	TATACCTTTCTTTAACCCT	1-4-1-11-2	TatacCtttctttaaccCT	690_5	-21.79	8115
  691	TTATACCTTTCTTTAAC	4-7-2-2-2	TTATacctttcTTtaAC	691_1	-18.49	8118
  691	TTATACCTTTCTTTAAC	3-8-1-1-4	TTAtacctttcTtTAAC	691_2	-18.07	8118
  692	TTATACCTTTCTTTAACCC	2-10-1-1-1-2-2	TTatacctttctTtAacCC	692_1	-21.94	8116
  692	TTATACCTTTCTTTAACCC	1-1-1-9-1-4-2	TtAtacctttctTtaacCC	692_2	-20.68	8116
  692	TTATACCTTTCTTTAACCC	1-4-1-7-1-3-2	TtataCctttcttTaacCC	692_3	-21.79	8116
  692	TTATACCTTTCTTTAACCC	1-3-2-8-2-1-2	TtatACctttctttAAcCC	692_4	-22.39	8116
  692	TTATACCTTTCTTTAACCC	1-1-1-2-1-9-1-1-2	TtAtaCctttctttaAcCC	692_5	-21.58	8116
  693	TTATACCTTTCTTTAACC	2-3-1-6-1-3-2	TTataCctttctTtaaCC	693_1	-19.80	8117
  693	TTATACCTTTCTTTAACC	1-1-1-1-2-6-1-3-2	TtAtACctttctTtaaCC	693_2	-19.25	8117
  693	TTATACCTTTCTTTAACC	1-3-2-7-2-1-2	TtatACctttcttTAaCC	693_3	-20.74	8117
  693	TTATACCTTTCTTTAACC	1-1-1-2-1-7-1-2-2	TtAtaCctttcttTaaCC	693_4	-19.08	8117
  693	TTATACCTTTCTTTAACC	1-2-1-1-1-8-4	TtaTaCctttctttAACC	693_5	-20.26	8117
  694	TTTATACCTTTCTTTAACC	2-1-1-8-2-3-2	TTTAtacctttcTTtaaCC	694_1	-20.72	8117
  694	TTTATACCTTTCTTTAACC	1-4-1-6-1-2-4	TttatAcctttcTttAACC	694_2	-20.33	8117
  694	TTTATACCTTTCTTTAACC	2-11-1-1-1-1-2	TTtatacctttctTtAaCC	694_3	-19.72	8117
  694	TTTATACCTTTCTTTAACC	1-1-2-9-1-3-2	TtTAtacctttctTtaaCC	694_4	-20.65	8117
  694	TTTATACCTTTCTTTAACC	1-3-2-7-1-3-2	TttaTAcctttctTtaaCC	694_5	-20.88	8117
  695	TTTATACCTTTCTTTAAC	3-9-3-1-2	TTTatacctttcTTTaAC	695_1	-18.74	8118
  695	TTTATACCTTTCTTTAAC	5-7-2-2-2	TTTATacctttcTTtaAC	695_2	-20.31	8118
  695	TTTATACCTTTCTTTAAC	1-1-3-7-2-2-2	TtTATacctttcTTtaAC	695_3	-18.98	8118
  695	TTTATACCTTTCTTTAAC	4-8-1-1-4	TTTAtacctttcTtTAAC	695_4	-19.89	8118
  695	TTTATACCTTTCTTTAAC	2-3-1-7-5	TTtatAcctttctTTAAC	695_5	-18.02	8118
  696	TTTTATACCTTTCTTTAAC	2-3-1-6-3-2-2	TTttaTacctttCTTtaAC	696_1	-19.79	8118
  696	TTTTATACCTTTCTTTAAC	1-1-2-8-2-1-1-1-2	TtTTatacctttCTtTaAC	696_2	-19.57	8118
  696	TTTTATACCTTTCTTTAAC	2-1-2-7-2-2-3	TTtTAtacctttCTttAAC	696_3	-20.28	8118
  696	TTTTATACCTTTCTTTAAC	3-9-1-1-5	TTTtatacctttCtTTAAC	696_4	-20.62	8118
  696	TTTTATACCTTTCTTTAAC	1-1-3-7-1-1-1-2-2	TtTTAtacctttCtTtaAC	696_5	-19.08	8118
  697	TGTACTTTCCTTTACCA	2-9-1-3-2	TGtactttcctTtacCA	697_1	-20.68	11462
  697	TGTACTTTCCTTTACCA	1-2-1-7-1-3-2	TgtActttcctTtacCA	697_2	-19.66	11462
  697	TGTACTTTCCTTTACCA	1-3-1-6-1-3-2	TgtaCtttcctTtacCA	697_3	-20.46	11462
  697	TGTACTTTCCTTTACCA	2-2-1-8-1-1-2	TGtaCtttcctttAcCA	697_4	-21.56	11462
  697	TGTACTTTCCTTTACCA	1-3-1-9-3	TgtaCtttcctttaCCA	697_5	-22.54	11462
  698	TTATACACCATCATTAT	4-7-3-1-2	TTATacaccatCATTAT	698_1	-21.13	11506
  698	TTATACACCATCATTAT	4-7-2-1-3	TTATacaccatCAtTAT	698_2	-21.64	11506
  698	TTATACACCATCATTAT	3-8-1-1-4	TTAtacaccatCaTTAT	698_3	-19.45	11506
  698	TTATACACCATCATTAT	2-1-2-7-5	TTaTAcaccatcATTAT	698_4	-20.61	11506
  698	TTATACACCATCATTAT	5-9-3	TTATAcaccatcatTAT	698_5	-20.74	11506
  699	TTATACACCATCATTATA	3-2-1-6-2-2-2	TTAtaCaccatcATtaTA	699_1	-19.38	11505
  699	TTATACACCATCATTATA	1-2-3-6-1-1-4	TtaTACaccatcAtTATA	699_2	-20.93	11505
  699	TTATACACCATCATTATA	4-1-1-7-2-1-2	TTATaCaccatcaTTaTA	699_3	-21.44	11505
  699	TTATACACCATCATTATA	2-1-2-8-1-1-3	TTaTAcaccatcaTtATA	699_4	-19.71	11505
  699	TTATACACCATCATTATA	3-2-1-8-4	TTAtaCaccatcatTATA	699_5	-20.75	11505
  700	TTTATACACCATCATTAT	2-1-2-7-3-1-2	TTtATacaccatCATtAT	700_1	-20.67	11506
  700	TTTATACACCATCATTAT	3-1-1-7-2-1-3	TTTaTacaccatCAtTAT	700_2	-21.52	11506
  700	TTTATACACCATCATTAT	1-3-2-6-2-1-3	TttaTAcaccatCAtTAT	700_3	-20.70	11506
  700	TTTATACACCATCATTAT	1-1-3-8-1-1-3	TtTATacaccatcAtTAT	700_4	-20.05	11506
  700	TTTATACACCATCATTAT	3-1-1-9-4	TTTaTacaccatcaTTAT	700_5	-20.34	11506
  701	TTTATACACCATCATTATA	4-8-1-1-2-1-2	TTTAtacaccatCaTTaTA	701_1	-21.57	11505
  701	TTTATACACCATCATTATA	2-2-1-7-1-2-4	TTtaTacaccatCatTATA	701_2	-21.05	11505
  701	TTTATACACCATCATTATA	1-1-1-1-1-8-2-1-3	TtTaTacaccatcATtATA	701_3	-19.83	11505
  701	TTTATACACCATCATTATA	2-2-2-7-2-2-2	TTtaTAcaccatcATtaTA	701_4	-20.24	11505
  701	TTTATACACCATCATTATA	1-1-3-10-1-1-2	TtTATacaccatcatTaTA	701_5	-20.30	11505
  702	ATTTATACACCATCATTAT	1-1-1-2-1-7-3-1-2	AtTtaTacaccatCATtAT	702_1	-20.07	11506
  702	ATTTATACACCATCATTAT	1-1-2-1-1-7-2-2-2	AtTTaTacaccatCAttAT	702_2	-20.07	11506
  702	ATTTATACACCATCATTAT	2-1-2-8-1-1-1-1-2	ATtTAtacaccatCaTtAT	702_3	-19.74	11506
  702	ATTTATACACCATCATTAT	2-3-1-7-1-2-3	ATttaTacaccatCatTAT	702_4	-20.07	11506
  702	ATTTATACACCATCATTAT	1-1-1-1-1-10-4	AtTtAtacaccatcaTTAT	702_5	-18.64	11506
  703	ATTTATACACCATCATTATA	1-4-1-7-1-2-4	AtttaTacaccatCatTATA	703_1	-21.05	11505
  703	ATTTATACACCATCATTATA	2-1-1-2-1-7-2-2-2	ATtTatAcaccatcATtaTA	703_2	-20.32	11505
  703	ATTTATACACCATCATTATA	1-1-1-2-1-8-1-1-1-1-2	AtTtaTacaccatcAtTaTA	703_3	-18.80	11505
  703	ATTTATACACCATCATTATA	1-2-3-8-1-1-1-1-2	AttTATacaccatcAtTaTA	703_4	-21.17	11505
  703	ATTTATACACCATCATTATA	3-1-1-9-1-2-3	ATTTAtacaccatcAttATA	703_5	-19.97	11505
  704	TATTTATACACCATCATTA	1-2-3-6-2-3-2	TatTTAtacaccATcatTA	704_1	-20.37	11507
  704	TATTTATACACCATCATTA	4-8-1-1-2-1-2	TATTtatacaccAtCAtTA	704_2	-21.70	11507
  704	TATTTATACACCATCATTA	1-1-1-1-1-7-1-1-1-1-3	TaTtTatacaccAtCaTTA	704_3	-19.16	11507
  704	TATTTATACACCATCATTA	2-2-1-8-2-2-2	TAttTatacaccaTCatTA	704_4	-19.98	11507
  704	TATTTATACACCATCATTA	2-2-1-10-4	TAttTatacaccatcATTA	704_5	-19.99	11507
  705	TATTTATACACCATCATTAT	2-2-1-1-1-7-2-2-2	TAttTaTacaccatCAttAT	705_1	-21.49	11506
  705	TATTTATACACCATCATTAT	2-1-1-10-1-1-4	TAtTtatacaccatCaTTAT	705_2	-21.44	11506
  705	TATTTATACACCATCATTAT	1-1-1-2-1-8-1-1-1-1-2	TaTttAtacaccatCaTtAT	705_3	-18.27	11506
  705	TATTTATACACCATCATTAT	2-1-2-9-1-3-2	TAtTTatacaccatCattAT	705_4	-19.97	11506
  705	TATTTATACACCATCATTAT	1-2-3-9-1-1-3	TatTTAtacaccatcAtTAT	705_5	-21.11	11506
  706	TTATTTATACACCATCATTA	2-3-1-7-1-1-1-1-3	TTattTatacaccAtCaTTA	706_1	-20.54	11507
  706	TTATTTATACACCATCATTA	1-1-2-1-1-7-1-2-4	TtATtTatacaccAtcATTA	706_2	-20.84	11507
  706	TTATTTATACACCATCATTA	1-1-1-2-1-8-2-2-2	TtAttTatacaccaTCatTA	706_3	-19.52	11507
  706	TTATTTATACACCATCATTA	1-2-3-8-1-1-1-1-2	TtaTTTatacaccaTcAtTA	706_4	-19.96	11507
  706	TTATTTATACACCATCATTA	3-1-1-11-1-1-2	TTAtTtatacaccatcAtTA	706_5	-19.63	11507
  707	ATTATTTATACACCATCAT	2-2-2-6-3-2-2	ATtaTTtatacaCCAtcAT	707_1	-22.41	11509
  707	ATTATTTATACACCATCAT	2-3-1-6-1-2-4	ATtatTtatacaCcaTCAT	707_2	-21.02	11509
  707	ATTATTTATACACCATCAT	1-1-1-1-1-8-3-1-2	AtTaTttatacacCATcAT	707_3	-20.01	11509
  707	ATTATTTATACACCATCAT	1-1-2-1-1-7-1-2-3	AtTAtTtatacacCatCAT	707_4	-20.30	11509
  707	ATTATTTATACACCATCAT	2-1-2-9-1-1-3	ATtATttatacaccAtCAT	707_5	-20.20	11509
  708	ATTATTTATACACCATCA	2-2-2-6-2-2-2	ATtaTTtatacaCCatCA	708_1	-20.96	11510
  708	ATTATTTATACACCATCA	3-1-1-7-1-1-4	ATTaTttatacaCcATCA	708_2	-21.19	11510
  708	ATTATTTATACACCATCA	1-1-3-7-1-3-2	AtTATttatacaCcatCA	708_3	-19.39	11510
  708	ATTATTTATACACCATCA	1-1-1-2-1-7-2-1-2	AtTatTtatacacCAtCA	708_4	-18.57	11510
  708	ATTATTTATACACCATCA	2-1-2-8-1-1-3	ATTATttatacacCaTCA	708_5	-19.79	11510
  709	ATTATTTATACACCATCATT	1-2-3-7-1-1-2-1-2	AttATTtatacacCaTCaTT	709_1	-20.97	11508
  709	ATTATTTATACACCATCATT	1-1-1-2-2-6-1-4-2	AtTatTTatacacCatcaTT	709_2	-19.29	11508
  709	ATTATTTATACACCATCATT	1-1-1-2-1-8-2-1-3	AtTatTtatacaccATcATT	709_3	-19.70	11508
  709	ATTATTTATACACCATCATT	3-1-1-9-1-1-1-1-2	ATTaTttatacaccAtCaTT	709_4	-20.09	11508
  709	ATTATTTATACACCATCATT	2-1-2-1-1-7-1-2-3	ATtATtTatacaccAtcATT	709_5	-20.67	11508
  710	ATTATTTATACACCATC	5-6-3-1-2	ATTATttatacACCaTC	710_1	-21.70	11511
  710	ATTATTTATACACCATC	5-6-2-1-3	ATTATttatacACcATC	710_2	-20.38	11511
  710	ATTATTTATACACCATC	2-2-1-7-5	ATtaTttatacaCCATC	710_3	-20.25	11511
  710	ATTATTTATACACCATC	1-1-2-8-5	AtTAtttatacaCCATC	710_4	-20.42	11511
  710	ATTATTTATACACCATC	5-8-4	ATTATttatacacCATC	710_5	-21.04	11511
  711	AATTATTTATACACCATC	2-2-2-6-3-1-2	AAttATttatacACCaTC	711_1	-18.93	11511
  711	AATTATTTATACACCATC	2-1-3-6-1-1-4	AAtTATttatacAcCATC	711_2	-20.18	11511
  711	AATTATTTATACACCATC	4-1-1-7-5	AATTaTttatacaCCATC	711_3	-22.24	11511
  711	AATTATTTATACACCATC	2-1-2-8-5	AAtTAtttatacaCCATC	711_4	-21.17	11511
  711	AATTATTTATACACCATC	1-1-4-7-2-1-2	AaTTATttatacaCCaTC	711_5	-20.58	11511
  712	AATTATTTATACACCATCA	1-2-1-1-1-6-3-2-2	AatTaTttatacACCatCA	712_1	-20.42	11510
  712	AATTATTTATACACCATCA	2-2-1-7-1-1-2-1-2	AAttAtttatacAcCAtCA	712_2	-18.54	11510
  712	AATTATTTATACACCATCA	1-1-3-7-1-2-4	AaTTAtttatacAccATCA	712_3	-20.67	11510
  712	AATTATTTATACACCATCA	2-1-2-8-2-1-3	AAtTAtttatacaCCaTCA	712_4	-22.20	11510
  712	AATTATTTATACACCATCA	3-1-1-8-1-2-3	AATtAtttatacaCcaTCA	712_5	-19.50	11510
  713	AAATTATTTATACACCATC	3-2-1-6-3-1-3	AAAttAtttataCACcATC	713_1	-19.21	11511
  713	AAATTATTTATACACCATC	1-2-3-6-3-2-2	AaaTTAtttataCACcaTC	713_2	-20.01	11511
  713	AAATTATTTATACACCATC	1-1-3-7-2-1-4	AaATTatttataCAcCATC	713_3	-21.68	11511
  713	AAATTATTTATACACCATC	2-1-2-7-1-1-2-1-2	AAaTTatttataCaCCaTC	713_4	-19.63	11511
  713	AAATTATTTATACACCATC	1-1-2-1-1-8-5	AaATtAtttatacaCCATC	713_5	-20.67	11511
  714	AAATTATTTATACACCAT	1-1-4-6-2-1-3	AaATTAtttataCAcCAT	714_1	-20.31	11512
  714	AAATTATTTATACACCAT	2-2-2-6-1-1-4	AAatTAtttataCaCCAT	714_2	-19.59	11512
  714	AAATTATTTATACACCAT	1-1-3-7-1-1-4	AaATTatttataCaCCAT	714_3	-20.00	11512
  714	AAATTATTTATACACCAT	4-9-5	AAATtatttatacACCAT	714_4	-19.36	11512
  714	AAATTATTTATACACCAT	3-1-2-7-5	AAAtTAtttatacACCAT	714_5	-19.98	11512
  715	AAAATTATTTATACACCAT	2-1-2-7-3-1-3	AAaATtatttatACAcCAT	715_1	-19.29	11512
  715	AAAATTATTTATACACCAT	1-3-2-6-2-1-4	AaaaTTatttatACaCCAT	715_2	-19.68	11512
  715	AAAATTATTTATACACCAT	3-2-1-6-1-1-5	AAAatTatttatAcACCAT	715_3	-19.27	11512
  715	AAAATTATTTATACACCAT	1-1-4-7-1-1-4	AaAATTatttataCaCCAT	715_4	-20.75	11512
  715	AAAATTATTTATACACCAT	2-1-2-9-5	AAaATtatttatacACCAT	715_5	-19.38	11512
  716	TAAAATTATTTATACACC	2-1-3-6-3-1-2	TAaAATtatttaTACaCC	716_1	-18.88	11514
  716	TAAAATTATTTATACACC	3-1-2-7-5	TAAaATtatttatACACC	716_2	-18.95	11514
  716	TAAAATTATTTATACACC	1-1-4-7-5	TaAAATtatttatACACC	716_3	-18.33	11514
  716	TAAAATTATTTATACACC	3-1-2-8-4	TAAaATtatttataCACC	716_4	-18.35	11514
  716	TAAAATTATTTATACACC	2-1-3-8-4	TAaAATtatttataCACC	716_5	-18.35	11514
  717	GTAAAATTATTTATACACC	2-1-3-6-4-1-2	GTaAAAttatttATACaCC	717_1	-21.68	11514
  717	GTAAAATTATTTATACACC	3-2-1-6-2-2-3	GTAaaAttatttATacACC	717_2	-20.00	11514
  717	GTAAAATTATTTATACACC	3-1-2-7-2-1-3	GTAaAAttatttaTAcACC	717_3	-20.86	11514
  717	GTAAAATTATTTATACACC	2-1-3-7-1-1-4	GTaAAAttatttaTaCACC	717_4	-21.11	11514
  717	GTAAAATTATTTATACACC	4-1-1-8-5	GTAAaAttatttatACACC	717_5	-21.46	11514
  718	GTAAAATTATTTATACAC	4-1-1-7-5	GTAAaAttatttaTACAC	718_1	-18.17	11515
  718	GTAAAATTATTTATACAC	3-1-2-7-5	GTAaAAttatttaTACAC	718_2	-18.17	11515
  719	GAGTATATTACCTCCA	3-10-3	GAGtatattacctCCA	719_1	-22.56	15162
  719	GAGTATATTACCTCCA	2-1-1-9-3	GAgTatattacctCCA	719_2	-22.24	15162
  719	GAGTATATTACCTCCA	2-11-3	GAgtatattacctCCA	719_3	-21.15	15162
  719	GAGTATATTACCTCCA	1-1-3-8-3	GaGTAtattacctCCA	719_4	-22.93	15162
  719	GAGTATATTACCTCCA	5-9-2	GAGTAtattacctcCA	719_5	-23.29	15162
  720	CTTTTCTATAATCTCAC	2-2-1-6-3-1-2	CTttTctataaTCTcAC	720_1	-18.54	30553
  720	CTTTTCTATAATCTCAC	3-8-2-1-3	CTTttctataaTCtCAC	720_2	-19.80	30553
  720	CTTTTCTATAATCTCAC	1-1-3-6-1-1-4	CtTTTctataaTcTCAC	720_3	-19.40	30553
  720	CTTTTCTATAATCTCAC	4-8-5	CTTTtctataatCTCAC	720_4	-21.37	30553
  720	CTTTTCTATAATCTCAC	1-3-1-7-5	CtttTctataatCTCAC	720_5	-18.92	30553
  721	CTTTTCTATAATCTCACA	2-3-1-6-1-1-1-1-2	CTtttCtataatCtCaCA	721_1	-20.17	30552
  721	CTTTTCTATAATCTCACA	1-1-1-1-2-6-1-2-3	CtTtTCtataatCtcACA	721_2	-20.15	30552
  721	CTTTTCTATAATCTCACA	1-2-1-1-1-7-2-1-2	CttTtCtataatcTCaCA	721_3	-19.50	30552
  721	CTTTTCTATAATCTCACA	1-1-3-8-1-1-3	CtTTTctataatcTcACA	721_4	-19.49	30552
  721	CTTTTCTATAATCTCACA	3-2-1-8-4	CTTttCtataatctCACA	721_5	-21.97	30552
  722	TCTTTTCTATAATCTCACA	1-1-3-7-1-1-1-1-3	TcTTTtctataaTcTcACA	722_1	-21.04	30552
  722	TCTTTTCTATAATCTCACA	1-4-1-6-1-2-1-1-2	TctttTctataaTctCaCA	722_2	-18.81	30552
  722	TCTTTTCTATAATCTCACA	2-2-1-8-1-2-3	TCttTtctataatCtcACA	722_3	-20.68	30552
  722	TCTTTTCTATAATCTCACA	2-1-1-9-1-3-2	TCtTttctataatCtcaCA	722_4	-20.13	30552
  722	TCTTTTCTATAATCTCACA	2-13-1-1-2	TCttttctataatctCaCA	722_5	-19.52	30552
  723	TCTTTTCTATAATCTCAC	2-1-1-8-2-2-2	TCtTttctataaTCtcAC	723_1	-18.51	30553
  723	TCTTTTCTATAATCTCAC	3-10-1-1-3	TCTtttctataatCtCAC	723_2	-20.36	30553
  723	TCTTTTCTATAATCTCAC	1-2-3-7-1-1-3	TctTTTctataatCtCAC	723_3	-19.57	30553
  723	TCTTTTCTATAATCTCAC	2-2-2-8-4	TCttTTctataatcTCAC	723_4	-20.57	30553
  723	TCTTTTCTATAATCTCAC	1-1-4-8-4	TcTTTTctataatcTCAC	723_5	-20.82	30553
  724	ATCTTTTCTATAATCTCACA	1-1-1-1-1-9-1-1-1-1-2	AtCtTttctataatCtCaCA	724_1	-20.93	30552
  724	ATCTTTTCTATAATCTCACA	1-1-1-11-1-2-3	AtCttttctataatCtcACA	724_2	-20.51	30552
  724	ATCTTTTCTATAATCTCACA	1-2-1-1-1-8-1-2-3	AtcttTtctataatCtcACA	724_3	-20.35	30552
  724	ATCTTTTCTATAATCTCACA	1-3-2-8-1-3-2	AtctTTtctataatCtcaCA	724_4	-20.10	30552
  724	ATCTTTTCTATAATCTCACA	1-1-1-2-1-10-1-1-2	AtCttTtctataatctCaCA	724_5	-19.95	30552
  725	ATCTTTTCTATAATCTCAC	1-1-1-9-1-1-1-1-3	AtCttttctataAtCtCAC	725_1	-19.62	30553
  725	ATCTTTTCTATAATCTCAC	1-2-2-7-1-1-1-1-3	AtcttttctataAtCtCAC	725_2	-19.97	30553
  725	ATCTTTTCTATAATCTCAC	1-1-2-1-1-7-2-2-2	AtCTtTtctataaTCtcAC	725_3	-19.83	30553
  725	ATCTTTTCTATAATCTCAC	1-2-1-1-1-9-4	AtcttTtctataatcTCAC	725_4	-19.36	30553
  725	ATCTTTTCTATAATCTCAC	3-13-3	ATCttttctataatctCAC	725_5	-20.25	30553
  726	ATCTTTTCTATAATCTCA	1-1-2-8-1-1-1-1-2	AtCTtttctataAtCtCA	726_1	-18.77	30554
  726	ATCTTTTCTATAATCTCA	3-1-1-7-1-2-3	ATCtTttctataAtcTCA	726_2	-20.03	30554
  726	ATCTTTTCTATAATCTCA	3-10-2-1-2	ATCttttctataaTCtCA	726_3	-20.31	30554
  726	ATCTTTTCTATAATCTCA	1-1-1-1-2-7-2-1-2	AtCtTTtctataaTCtCA	726_4	-19.49	30554
  726	ATCTTTTCTATAATCTCA	1-1-3-9-4	AtCTTttctataatCTCA	726_5	-21.14	30554
  727	CATCTTTTCTATAATCTCAC	2-11-1-1-1-2-2	CAtcttttctataAtCtcAC	727_1	-19.86	30553
  727	CATCTTTTCTATAATCTCAC	1-1-2-9-1-1-1-2-2	CaTCttttctataAtCtcAC	727_2	-20.49	30553
  727	CATCTTTTCTATAATCTCAC	1-3-1-1-1-8-1-1-3	CatcTtTtctataatCtCAC	727_3	-20.97	30553
  727	CATCTTTTCTATAATCTCAC	1-2-1-1-1-9-1-2-2	CatCtTttctataatCtcAC	727_4	-19.35	30553
  727	CATCTTTTCTATAATCTCAC	2-1-1-2-1-10-3	CAtCttTtctataatctCAC	727_5	-21.92	30553
  728	CATCTTTTCTATAATCTCA	1-3-1-7-2-1-1-1-2	CatcTtttctatAAtCtCA	728_1	-19.26	30554
  728	CATCTTTTCTATAATCTCA	2-3-1-6-2-2-3	CAtctTttctatAAtcTCA	728_2	-20.74	30554
  728	CATCTTTTCTATAATCTCA	1-2-1-8-1-2-1-1-2	CatCttttctatAatCtCA	728_3	-19.21	30554
  728	CATCTTTTCTATAATCTCA	2-1-1-1-1-9-1-1-2	CAtCtTttctataatCtCA	728_4	-20.86	30554
  728	CATCTTTTCTATAATCTCA	1-1-2-13-2	CaTCttttctataatctCA	728_5	-19.23	30554
  729	TCATCTTTTCTATAATCTCA	1-1-1-2-1-7-2-1-1-1-2	TcAtcTtttctatAAtCtCA	729_1	-20.53	30554
  729	TCATCTTTTCTATAATCTCA	2-4-1-6-2-3-2	TCatctTttctatAAtctCA	729_2	-20.57	30554
  729	TCATCTTTTCTATAATCTCA	2-2-1-8-1-2-1-1-2	TCatCttttctatAatCtCA	729_3	-21.70	30554
  729	TCATCTTTTCTATAATCTCA	3-13-1-1-2	TCAtcttttctataatCtCA	729_4	-22.07	30554
  729	TCATCTTTTCTATAATCTCA	3-1-1-13-2	TCAtCttttctataatctCA	729_5	-22.07	30554
  730	TCATCTTTTCTATAATCTC	3-2-1-7-2-2-2	TCAtcTtttctatAAtcTC	730_1	-20.15	30555
  730	TCATCTTTTCTATAATCTC	3-1-1-8-1-3-2	TCAtCttttctatAatcTC	730_2	-20.09	30555
  730	TCATCTTTTCTATAATCTC	2-2-1-9-1-2-2	TCatCttttctataAtcTC	730_3	-18.83	30555
  730	TCATCTTTTCTATAATCTC	3-13-3	TCAtcttttctataatCTC	730_4	-20.65	30555
  730	TCATCTTTTCTATAATCTC	2-2-2-10-3	TCatCTtttctataatCTC	730_5	-21.35	30555
  731	GTCATCTTTTCTATAATC	1-1-1-2-1-6-3-1-2	GtCatCttttctATAaTC	731_1	-19.76	30557
  731	GTCATCTTTTCTATAATC	1-1-1-1-2-6-1-2-3	GtCaTCttttctAtaATC	731_2	-19.19	30557
  731	GTCATCTTTTCTATAATC	4-9-1-2-2	GTCAtcttttctaTaaTC	731_3	-20.42	30557
  731	GTCATCTTTTCTATAATC	3-2-1-8-4	GTCatCttttctatAATC	731_4	-20.51	30557
  731	GTCATCTTTTCTATAATC	1-1-4-10-2	GtCATCttttctataaTC	731_5	-20.23	30557
  732	TGTCATCTTTTCTATAAT	2-1-1-8-2-1-3	TGtCatcttttcTAtAAT	732_1	-19.36	30558
  732	TGTCATCTTTTCTATAAT	2-1-2-7-2-2-2	TGtCAtcttttcTAtaAT	732_2	-20.51	30558
  732	TGTCATCTTTTCTATAAT	1-1-3-7-1-3-2	TgTCAtcttttcTataAT	732_3	-19.51	30558
  732	TGTCATCTTTTCTATAAT	4-10-4	TGTCatcttttctaTAAT	732_4	-21.42	30558
  732	TGTCATCTTTTCTATAAT	2-2-1-9-4	TGtcAtcttttctaTAAT	732_5	-18.57	30558
  733	ACTTAATTATACTTCCA	5-6-2-2-2	ACTTAattataCTtcCA	733_1	-21.55	30664
  733	ACTTAATTATACTTCCA	2-1-2-6-1-2-3	ACtTAattataCttCCA	733_2	-21.02	30664
  733	ACTTAATTATACTTCCA	1-2-2-7-5	ActTAattatacTTCCA	733_3	-20.65	30664
  733	ACTTAATTATACTTCCA	4-8-1-1-3	ACTTaattatacTtCCA	733_4	-21.09	30664
  733	ACTTAATTATACTTCCA	1-1-1-1-1-8-4	AcTtAattatactTCCA	733_5	-18.37	30664
  734	CACTTAATTATACTTCC	2-1-2-6-2-2-2	CAcTTaattatACttCC	734_1	-20.10	30665
  734	CACTTAATTATACTTCC	5-6-1-2-3	CACTTaattatActTCC	734_2	-21.76	30665
  734	CACTTAATTATACTTCC	1-1-1-1-1-7-2-1-2	CaCtTaattataCTtCC	734_3	-19.09	30665
  734	CACTTAATTATACTTCC	1-1-3-7-1-1-3	CaCTTaattataCtTCC	734_4	-20.59	30665
  734	CACTTAATTATACTTCC	2-1-2-8-4	CAcTTaattatacTTCC	734_5	-20.52	30665
  735	CACTTAATTATACTTCCA	2-2-1-7-2-1-3	CActTaattataCTtCCA	735_1	-22.96	30664
  735	CACTTAATTATACTTCCA	2-1-1-1-1-6-1-3-2	CAcTtAattataCttcCA	735_2	-19.31	30664
  735	CACTTAATTATACTTCCA	1-1-3-8-1-1-3	CaCTTaattatacTtCCA	735_3	-22.43	30664
  735	CACTTAATTATACTTCCA	1-1-1-1-2-7-1-2-2	CaCtTAattatacTtcCA	735_4	-19.51	30664
  735	CACTTAATTATACTTCCA	2-2-1-9-4	CActTaattatactTCCA	735_5	-21.76	30664
  736	ACACTTAATTATACTTCCA	1-1-2-1-1-6-2-3-2	AcACtTaattatACttcCA	736_1	-20.93	30664
  736	ACACTTAATTATACTTCCA	2-2-1-7-1-1-1-2-2	ACacTtaattatAcTtcCA	736_2	-19.38	30664
  736	ACACTTAATTATACTTCCA	1-1-1-1-1-8-1-2-3	AcAcTtaattataCttCCA	736_3	-21.10	30664
  736	ACACTTAATTATACTTCCA	1-1-1-2-1-9-4	AcActTaattatactTCCA	736_4	-21.31	30664
  736	ACACTTAATTATACTTCCA	2-2-2-11-2	ACacTTaattatacttcCA	736_5	-19.91	30664
  737	ACACTTAATTATACTTCC	1-3-1-7-2-1-3	AcacTtaattatACtTCC	737_1	-19.24	30665
  737	ACACTTAATTATACTTCC	1-1-1-1-2-6-2-2-2	AcAcTTaattatACttCC	737_2	-19.64	30665
  737	ACACTTAATTATACTTCC	2-1-2-7-1-1-1-1-2	ACaCTtaattatAcTtCC	737_3	-20.12	30665
  737	ACACTTAATTATACTTCC	3-2-1-8-4	ACActTaattatacTTCC	737_4	-21.53	30665
  737	ACACTTAATTATACTTCC	1-1-2-1-1-9-3	AcACtTaattatactTCC	737_5	-19.40	30665
  738	ACACTTAATTATACTTC	5-7-5	ACACTtaattatACTTC	738_1	-20.47	30666
  738	ACACTTAATTATACTTC	3-1-1-7-5	ACAcTtaattatACTTC	738_2	-18.40	30666
  738	ACACTTAATTATACTTC	2-1-2-7-5	ACaCTtaattatACTTC	738_3	-18.51	30666
  738	ACACTTAATTATACTTC	5-7-2-1-2	ACACTtaattatACtTC	738_4	-18.77	30666
  738	ACACTTAATTATACTTC	5-7-1-1-3	ACACTtaattatAcTTC	738_5	-18.40	30666
  738	ACACTTAATTATACTTC	5-8-4	ACACTtaattataCTTC	738_6	-19.88	30666
  739	TACACTTAATTATACTTCC	3-2-1-7-2-2-2	TACacTtaattatACttCC	739_1	-21.57	30665
  739	TACACTTAATTATACTTCC	1-4-1-7-1-1-4	TacacTtaattatAcTTCC	739_2	-19.87	30665
  739	TACACTTAATTATACTTCC	1-2-3-8-1-2-2	TacACTtaattataCttCC	739_3	-20.88	30665
  739	TACACTTAATTATACTTCC	4-11-4	TACActtaattatacTTCC	739_4	-23.04	30665
  739	TACACTTAATTATACTTCC	2-1-1-1-1-10-3	TAcAcTtaattatactTCC	739_5	-20.03	30665
  740	TACACTTAATTATACTTC	4-1-1-7-5	TACAcTtaattatACTTC	740_1	-20.63	30666
  740	TACACTTAATTATACTTC	3-1-2-7-5	TACaCTtaattatACTTC	740_2	-20.74	30666
  740	TACACTTAATTATACTTC	2-1-3-7-5	TAcACTtaattatACTTC	740_3	-20.21	30666
  740	TACACTTAATTATACTTC	3-1-2-8-4	TACaCTtaattataCTTC	740_4	-20.14	30666
  740	TACACTTAATTATACTTC	1-1-4-8-4	TaCACTtaattataCTTC	740_5	-20.48	30666
  741	TTACACTTAATTATACTTC	2-1-2-7-4-1-2	TTaCActtaattATACtTC	741_1	-21.41	30666
  741	TTACACTTAATTATACTTC	5-7-3-1-3	TTACActtaattATAcTTC	741_2	-22.67	30666
  741	TTACACTTAATTATACTTC	4-1-1-6-2-1-4	TTACaCttaattATaCTTC	741_3	-22.54	30666
  741	TTACACTTAATTATACTTC	2-1-2-7-2-1-4	TTaCActtaattATaCTTC	741_4	-21.48	30666
  741	TTACACTTAATTATACTTC	5-7-1-1-5	TTACActtaattAtACTTC	741_5	-22.04	30666
  742	TTACACTTAATTATACTT	5-7-3-1-2	TTACActtaattATAcTT	742_1	-20.18	30667
  742	TTACACTTAATTATACTT	5-7-2-1-3	TTACActtaattATaCTT	742_2	-20.62	30667
  742	TTACACTTAATTATACTT	5-7-1-1-4	TTACActtaattAtACTT	742_3	-19.54	30667
  743	TTTACACTTAATTATACTT	4-1-1-6-4-1-2	TTTAcActtaatTATAcTT	743_1	-21.26	30667
  743	TTTACACTTAATTATACTT	3-1-2-6-3-1-3	TTTaCActtaatTATaCTT	743_2	-22.57	30667
  743	TTTACACTTAATTATACTT	4-8-2-1-4	TTTAcacttaatTAtACTT	743_3	-20.48	30667
  743	TTTACACTTAATTATACTT	1-1-4-6-2-2-3	TtTACActtaatTAtaCTT	743_4	-21.20	30667
  743	TTTACACTTAATTATACTT	2-2-2-6-1-1-5	TTtaCActtaatTaTACTT	743_5	-21.02	30667
  744	TTTACACTTAATTATACT	3-1-2-6-3-1-2	TTTaCActtaatTATaCT	744_1	-20.75	30668
  744	TTTACACTTAATTATACT	1-1-4-6-3-1-2	TtTACActtaatTATaCT	744_2	-21.06	30668
  744	TTTACACTTAATTATACT	2-1-3-6-2-1-3	TTtACActtaatTAtACT	744_3	-19.03	30668
  744	TTTACACTTAATTATACT	4-8-1-1-4	TTTAcacttaatTaTACT	744_4	-19.42	30668
  744	TTTACACTTAATTATACT	1-1-1-1-2-6-1-1-4	TtTaCActtaatTaTACT	744_5	-19.12	30668
  745	ATTTACACTTAATTATACT	4-1-1-6-4-1-2	ATTTaCacttaaTTATaCT	745_1	-22.20	30668
  745	ATTTACACTTAATTATACT	2-1-3-6-3-1-3	ATtTACacttaaTTAtACT	745_2	-21.43	30668
  745	ATTTACACTTAATTATACT	5-7-2-1-4	ATTTAcacttaaTTaTACT	745_3	-22.44	30668
  745	ATTTACACTTAATTATACT	1-2-3-6-2-1-4	AttTACacttaaTTaTACT	745_4	-20.95	30668
  745	ATTTACACTTAATTATACT	3-1-2-6-1-1-5	ATTTACacttaaTtATACT	745_5	-20.92	30668
  746	ATTTACACTTAATTATAC	5-8-5	ATTTAcacttaatTATAC	746_1	-19.94	30669
  746	ATTTACACTTAATTATAC	4-1-1-7-5	ATTTaCacttaatTATAC	746_2	-19.40	30669
  746	ATTTACACTTAATTATAC	2-1-3-7-5	ATtTACacttaatTATAC	746_3	-19.70	30669
  747	AATTTACACTTAATTATAC	3-1-2-6-3-1-3	AATtTAcacttaATTaTAC	747_1	-19.51	30669
  747	AATTTACACTTAATTATAC	1-1-4-6-3-1-3	AaTTTAcacttaATTaTAC	747_2	-19.51	30669
  747	AATTTACACTTAATTATAC	4-8-2-1-4	AATTtacacttaATTATAC	747_3	-18.04	30669
  747	AATTTACACTTAATTATAC	5-7-1-1-5	AATTTacacttaAtTATAC	747_4	-19.79	30669
  747	AATTTACACTTAATTATAC	2-1-3-6-1-1-5	AAtTTAcacttaAtTATAC	747_5	-19.26	30669
  748	AATTTACACTTAATTATACT	3-2-2-6-4-1-2	AATttACacttaaTTATaCT	748_1	-21.50	30668
  748	AATTTACACTTAATTATACT	5-1-1-6-3-1-3	AATTTaCacttaaTTAtACT	748_2	-21.87	30668
  748	AATTTACACTTAATTATACT	3-1-3-6-2-1-4	AATtTACacttaaTTaTACT	748_3	-22.95	30668
  748	AATTTACACTTAATTATACT	1-1-4-7-2-1-1-1-2	AaTTTAcacttaaTTaTaCT	748_4	-20.23	30668
  748	AATTTACACTTAATTATACT	2-1-2-1-1-6-1-1-5	AAtTTaCacttaaTtATACT	748_5	-20.55	30668
  749	TAATTTACACTTAATTATAC	2-1-4-6-4-1-2	TAaTTTAcacttaATTAtAC	749_1	-20.98	30669
  749	TAATTTACACTTAATTATAC	5-8-3-1-3	TAATTtacacttaATTaTAC	749_2	-20.60	30669
  749	TAATTTACACTTAATTATAC	2-2-3-6-3-1-3	TAatTTAcacttaATTaTAC	749_3	-20.80	30669
  749	TAATTTACACTTAATTATAC	4-1-2-6-2-1-4	TAATtTAcacttaATTATAC	749_4	-21.41	30669
  749	TAATTTACACTTAATTATAC	1-1-1-1-2-7-1-1-5	TaAtTTacacttaAtTATAC	749_5	-18.92	30669
  750	TAATTTACACTTAATTAT	5-8-5	TAATTtacacttaATTAT	750_1	-18.27	30671
  750	TAATTTACACTTAATTAT	4-1-1-7-5	TAATtTacacttaATTAT	750_2	-18.18	30671
  750	TAATTTACACTTAATTAT	2-1-3-7-5	TAaTTTacacttaATTAT	750_3	-18.18	30671
  750	TAATTTACACTTAATTAT	1-1-4-7-5	TaATTTacacttaATTAT	750_4	-18.16	30671
  751	TAATTTACACTTAATTATA	5-7-4-1-2	TAATTtacacttAATTaTA	751_1	-18.87	30670
  751	TAATTTACACTTAATTATA	5-7-2-1-4	TAATTtacacttAAtTATA	751_2	-19.05	30670
  751	TAATTTACACTTAATTATA	3-1-2-6-2-1-4	TAAtTTacacttAAtTATA	751_3	-18.54	30670
  751	TAATTTACACTTAATTATA	4-1-1-6-1-1-5	TAATtTacacttAaTTATA	751_4	-19.40	30670
  751	TAATTTACACTTAATTATA	2-1-3-6-1-1-5	TAaTTTacacttAaTTATA	751_5	-19.41	30670
  752	TTAATTTACACTTAATTATA	3-1-3-6-4-1-2	TTAaTTTacacttAATTaTA	752_1	-20.61	30670
  752	TTAATTTACACTTAATTATA	5-1-1-6-3-1-3	TTAATtTacacttAATtATA	752_2	-20.28	30670
  752	TTAATTTACACTTAATTATA	2-1-4-6-2-1-4	TTaATTTacacttAAtTATA	752_3	-20.77	30670
  752	TTAATTTACACTTAATTATA	3-2-2-6-1-1-5	TTAatTTacacttAaTTATA	752_4	-20.28	30670
  752	TTAATTTACACTTAATTATA	4-1-1-8-1-1-4	TTAAtTtacacttaAtTATA	752_5	-18.80	30670
  753	TTAATTTACACTTAATTAT	4-1-1-6-3-1-3	TTAAtTtacactTAAtTAT	753_1	-18.65	30671
  753	TTAATTTACACTTAATTAT	3-1-2-6-2-1-4	TTAaTTtacactTAaTTAT	753_2	-19.52	30671
  753	TTAATTTACACTTAATTAT	2-1-2-7-2-1-4	TTaATttacactTAaTTAT	753_3	-18.68	30671
  753	TTAATTTACACTTAATTAT	5-7-1-1-5	TTAATttacactTaATTAT	753_4	-20.00	30671
  753	TTAATTTACACTTAATTAT	2-1-3-6-1-1-5	TTaATTtacactTaATTAT	753_5	-19.47	30671
  754	TTTAATTTACACTTAATTA	3-1-2-6-3-1-3	TTTaATttacacTTAaTTA	754_1	-19.46	30672
  754	TTTAATTTACACTTAATTA	5-7-2-1-4	TTTAAtttacacTTaATTA	754_2	-19.54	30672
  754	TTTAATTTACACTTAATTA	4-1-1-6-2-1-4	TTTAaTttacacTTaATTA	754_3	-19.46	30672
  754	TTTAATTTACACTTAATTA	1-1-1-1-2-6-2-1-4	TtTaATttacacTTaATTA	754_4	-18.11	30672
  754	TTTAATTTACACTTAATTA	1-1-4-7-3-1-2	TtTAATttacactTAAtTA	754_5	-18.02	30672
  755	TTTAATTTACACTTAATTAT	4-1-2-6-3-1-3	TTTAaTTtacactTAAtTAT	755_1	-20.90	30671
  755	TTTAATTTACACTTAATTAT	3-1-2-7-2-1-4	TTTaATttacactTAaTTAT	755_2	-20.50	30671
  755	TTTAATTTACACTTAATTAT	1-1-5-6-2-1-4	TtTAATTtacactTAaTTAT	755_3	-21.34	30671
  755	TTTAATTTACACTTAATTAT	5-8-1-1-5	TTTAAtttacactTaATTAT	755_4	-20.58	30671
  755	TTTAATTTACACTTAATTAT	2-2-3-6-1-1-5	TTtaATTtacactTaATTAT	755_5	-20.05	30671
  756	ATTTAATTTACACTTAATTA	5-1-1-6-4-1-2	ATTTAaTttacacTTAAtTA	756_1	-21.11	30672
  756	ATTTAATTTACACTTAATTA	3-2-2-6-3-1-3	ATTtaATttacacTTAaTTA	756_2	-20.29	30672
  756	ATTTAATTTACACTTAATTA	4-1-2-6-2-1-4	ATTTaATttacacTTaATTA	756_3	-21.50	30672
  756	ATTTAATTTACACTTAATTA	2-1-4-6-2-2-3	ATtTAATttacacTTaaTTA	756_4	-20.39	30672
  756	ATTTAATTTACACTTAATTA	2-1-4-8-5	ATtTAATttacacttAATTA	756_5	-20.08	30672
  757	ATTTAATTTACACTTAATT	5-7-3-1-3	ATTTAatttacaCTTaATT	757_1	-20.52	30673
  757	ATTTAATTTACACTTAATT	4-1-1-7-2-1-3	ATTTaAtttacacTTaATT	757_2	-18.02	30673
  757	ATTTAATTTACACTTAATT	2-1-3-7-2-1-3	ATtTAAtttacacTTaATT	757_3	-18.04	30673
  757	ATTTAATTTACACTTAATT	4-1-1-8-5	ATTTaAtttacactTAATT	757_4	-18.34	30673
  757	ATTTAATTTACACTTAATT	2-1-3-8-5	ATtTAAtttacactTAATT	757_5	-18.37	30673
  758	TATTTAATTTACACTTAAT	3-1-2-6-4-1-2	TATtTAatttacACTTaAT	758_1	-20.16	30674
  758	TATTTAATTTACACTTAAT	2-1-3-6-2-1-4	TAtTTAatttacACtTAAT	758_2	-19.37	30674
  758	TATTTAATTTACACTTAAT	1-1-4-6-2-1-4	TaTTTAatttacACtTAAT	758_3	-19.19	30674
  758	TATTTAATTTACACTTAAT	3-1-2-6-1-1-5	TATtTAatttacAcTTAAT	758_4	-19.44	30674
  758	TATTTAATTTACACTTAAT	2-1-3-6-1-1-5	TAtTTAatttacAcTTAAT	758_5	-19.00	30674
  759	TATTTAATTTACACTTAATT	2-1-4-6-4-1-2	TAtTTAAtttacaCTTAaTT	759_1	-21.54	30673
  759	TATTTAATTTACACTTAATT	5-1-1-6-3-1-3	TATTTaAtttacaCTTaATT	759_2	-21.92	30673
  759	TATTTAATTTACACTTAATT	4-1-2-7-3-1-2	TATTTAAtttacacTTAaTT	759_3	-19.35	30673
  759	TATTTAATTTACACTTAATT	3-1-3-7-2-1-3	TATtTAAtttacacTTaATT	759_4	-20.28	30673
  759	TATTTAATTTACACTTAATT	2-1-4-8-5	TAtTTAAtttacactTAATT	759_5	-20.16	30673
  760	CTATTTAATTTACACTT	5-6-1-1-4	CTATTtaatttAcACTT	760_1	-19.07	30677
  760	CTATTTAATTTACACTT	5-7-5	CTATTtaatttaCACTT	760_2	-20.97	30677
  760	CTATTTAATTTACACTT	2-2-1-7-5	CTatTtaatttaCACTT	760_3	-18.08	30677
  760	CTATTTAATTTACACTT	5-7-2-1-2	CTATTtaatttaCAcTT	760_4	-18.90	30677
  760	CTATTTAATTTACACTT	5-7-1-1-3	CTATTtaatttaCaCTT	760_5	-19.01	30677
  761	CTATTTAATTTACACTTAA	2-1-3-6-4-1-2	CTaTTTaatttaCACTTAA	761_1	-20.98	30675
  761	CTATTTAATTTACACTTAA	3-1-2-6-3-1-3	CTAtTTaatttaCACtTAA	761_2	-21.73	30675
  761	CTATTTAATTTACACTTAA	4-1-1-6-2-1-4	CTATtTaatttaCAcTTAA	761_3	-21.80	30675
  761	CTATTTAATTTACACTTAA	5-7-2-2-3	CTATTtaatttaCActTAA	761_4	-20.86	30675
  761	CTATTTAATTTACACTTAA	2-1-3-6-1-1-5	CTaTTTaatttaCaCTTAA	761_5	-21.29	30675
  762	CTATTTAATTTACACTTA	5-7-3-1-2	CTATTtaatttaCACtTA	762_1	-21.50	30676
  762	CTATTTAATTTACACTTA	3-2-1-6-3-1-2	CTAttTaatttaCACtTA	762_2	-20.17	30676
  762	CTATTTAATTTACACTTA	3-1-1-7-2-1-3	CTAtTtaatttaCAcTTA	762_3	-19.37	30676
  762	CTATTTAATTTACACTTA	2-1-3-6-2-1-3	CTaTTTaatttaCAcTTA	762_4	-20.43	30676
  762	CTATTTAATTTACACTTA	2-1-3-6-1-1-4	CTaTTTaatttaCaCTTA	762_5	-20.54	30676
  763	CTATTTAATTTACACTTAAT	2-1-4-6-3-2-2	CTaTTTAatttacACTtaAT	763_1	-21.79	30674
  763	CTATTTAATTTACACTTAAT	4-1-2-6-2-1-4	CTATtTAatttacACtTAAT	763_2	-23.29	30674
  763	CTATTTAATTTACACTTAAT	1-2-4-6-1-1-5	CtaTTTAatttacAcTTAAT	763_3	-20.68	30674
  763	CTATTTAATTTACACTTAAT	3-1-3-6-1-1-2-1-2	CTAtTTAatttacAcTTaAT	763_4	-21.14	30674
  763	CTATTTAATTTACACTTAAT	5-1-1-7-3-1-2	CTATTtAatttacaCTTaAT	763_5	-22.14	30674
  764	TCTATTTAATTTACACTTA	2-1-3-6-4-1-2	TCtATTtaatttACACtTA	764_1	-21.94	30676
  764	TCTATTTAATTTACACTTA	4-1-1-6-3-1-3	TCTAtTtaatttACAcTTA	764_2	-22.47	30676
  764	TCTATTTAATTTACACTTA	3-1-2-7-2-1-3	TCTaTTtaatttaCAcTTA	764_3	-21.69	30676
  764	TCTATTTAATTTACACTTA	1-1-4-7-2-2-2	TcTATTtaatttaCActTA	764_4	-20.33	30676
  764	TCTATTTAATTTACACTTA	3-2-1-7-1-1-4	TCTatTtaatttaCaCTTA	764_5	-20.85	30676
  765	TCTATTTAATTTACACTT	3-2-1-6-2-1-3	TCTatTtaatttACaCTT	765_1	-19.21	30677
  765	TCTATTTAATTTACACTT	3-1-2-7-5	TCTaTTtaatttaCACTT	765_2	-21.53	30677
  765	TCTATTTAATTTACACTT	2-1-3-7-5	TCtATTtaatttaCACTT	765_3	-20.81	30677
  765	TCTATTTAATTTACACTT	4-1-1-7-2-1-2	TCTAtTtaatttaCAcTT	765_4	-19.64	30677
  765	TCTATTTAATTTACACTT	1-1-4-7-2-1-2	TcTATTtaatttaCAcTT	765_5	-19.12	30677
  766	TCTATTTAATTTACACTTAA	2-1-2-1-1-6-3-2-2	TCtATtTaatttaCACttAA	766_1	-20.25	30675
  766	TCTATTTAATTTACACTTAA	4-1-1-7-2-1-4	TCTAtTtaatttaCAcTTAA	766_2	-22.62	30675
  766	TCTATTTAATTTACACTTAA	1-1-1-1-3-6-2-2-3	TcTaTTTaatttaCActTAA	766_3	-20.38	30675
  766	TCTATTTAATTTACACTTAA	3-1-2-7-1-1-2-1-2	TCTaTTtaatttaCaCTTAA	766_4	-20.27	30675
  766	TCTATTTAATTTACACTTAA	2-3-2-6-1-1-1-1-3	TCtatTTaatttaCaCtTAA	766_5	-19.51	30675
  767	ATCTATTTAATTTACACTT	2-1-2-7-4-1-2	ATcTAtttaattTACAcTT	767_1	-21.49	30677
  767	ATCTATTTAATTTACACTT	1-1-4-6-3-1-3	AtCTATttaattTACaCTT	767_2	-23.18	30677
  767	ATCTATTTAATTTACACTT	4-1-1-6-2-1-4	ATCTaTttaattTAcACTT	767_3	-22.64	30677
  767	ATCTATTTAATTTACACTT	5-7-2-2-3	ATCTAtttaattTAcaCTT	767_4	-22.78	30677
  767	ATCTATTTAATTTACACTT	1-1-4-6-1-1-5	AtCTATttaattTaCACTT	767_5	-23.52	30677
  768	ATCTATTTAATTTACACTTA	1-2-4-6-2-1-1-1-2	AtcTATTtaatttACaCtTA	768_1	-21.10	30676
  768	ATCTATTTAATTTACACTTA	1-1-3-1-1-6-1-1-5	AtCTAtTtaatttAcACTTA	768_2	-22.17	30676
  768	ATCTATTTAATTTACACTTA	3-2-2-6-1-1-2-1-2	ATCtaTTtaatttAcACtTA	768_3	-20.60	30676
  768	ATCTATTTAATTTACACTTA	1-1-2-1-2-7-2-2-2	AtCTaTTtaatttaCActTA	768_4	-20.80	30676
  768	ATCTATTTAATTTACACTTA	3-1-1-1-1-7-1-2-3	ATCtAtTtaatttaCacTTA	768_5	-19.72	30676
  769	TATCTATTTAATTTACACTT	1-1-2-1-2-6-4-1-2	TaTCTATttaattTACAcTT	769_1	-22.65	30677
  769	TATCTATTTAATTTACACTT	2-1-1-1-2-6-2-1-4	TAtCtATttaattTAcACTT	769_2	-22.23	30677
  769	TATCTATTTAATTTACACTT	2-1-4-6-2-3-2	TAtCTATttaattTAcacTT	769_3	-22.66	30677
  769	TATCTATTTAATTTACACTT	1-3-3-6-1-1-5	TatcTATttaattTaCACTT	769_4	-22.96	30677
  769	TATCTATTTAATTTACACTT	1-1-3-1-1-6-1-3-3	TaTCTaTttaattTacaCTT	769_5	-21.15	30677
  770	TATCTATTTAATTTACACT	2-1-3-6-3-1-3	TAtCTAtttaatTTAcACT	770_1	-22.62	30678
  770	TATCTATTTAATTTACACT	1-1-4-6-3-1-3	TaTCTAtttaatTTAcACT	770_2	-22.62	30678
  770	TATCTATTTAATTTACACT	2-2-2-6-2-1-4	TAtcTAtttaatTTaCACT	770_3	-21.84	30678
  770	TATCTATTTAATTTACACT	1-2-3-6-1-1-5	TatCTAtttaatTtACACT	770_4	-21.72	30678
  770	TATCTATTTAATTTACACT	4-1-1-7-2-1-3	TATCtAtttaattTAcACT	770_5	-21.09	30678
  771	TTATCTATTTAATTTACACT	2-4-1-6-4-1-2	TTatctAtttaatTTACaCT	771_1	-20.22	30678
  771	TTATCTATTTAATTTACACT	2-2-3-6-3-2-2	TTatCTAtttaatTTAcaCT	771_2	-22.76	30678
  771	TTATCTATTTAATTTACACT	1-1-5-6-2-2-3	TtATCTAtttaatTTacACT	771_3	-22.87	30678
  771	TTATCTATTTAATTTACACT	2-2-3-6-1-2-4	TTatCTAtttaatTtaCACT	771_4	-22.94	30678
  771	TTATCTATTTAATTTACACT	5-1-1-7-1-2-3	TTATCtAtttaattTacACT	771_5	-21.68	30678
  772	TTTATCTATTTAATTTACA	1-1-3-7-4-1-2	TtTATctatttaATTTaCA	772_1	-19.96	30680
  772	TTTATCTATTTAATTTACA	4-1-1-6-3-2-2	TTTAtCtatttaATTtaCA	772_2	-19.70	30680
  772	TTTATCTATTTAATTTACA	3-1-2-6-2-1-4	TTTaTCtatttaATtTACA	772_3	-21.24	30680
  772	TTTATCTATTTAATTTACA	5-7-2-2-3	TTTATctatttaATttACA	772_4	-19.82	30680
  772	TTTATCTATTTAATTTACA	1-1-4-6-1-1-5	TtTATCtatttaAtTTACA	772_5	-21.42	30680
  773	TTTTATCTATTTAATTTAC	2-1-3-6-3-1-3	TTtTATctatttAATtTAC	773_1	-19.10	30681
  773	TTTTATCTATTTAATTTAC	1-1-4-6-2-1-4	TtTTATctatttAAtTTAC	773_2	-18.66	30681
  773	TTTTATCTATTTAATTTAC	3-1-2-6-1-1-5	TTTTATctatttAaTTTAC	773_3	-18.15	30681
  773	TTTTATCTATTTAATTTAC	1-2-3-6-1-1-5	TttTATctatttAaTTTAC	773_4	-18.29	30681
  773	TTTTATCTATTTAATTTAC	2-1-3-6-1-2-4	TTtTATctatttAatTTAC	773_5	-18.15	30681
  774	TTTTATCTATTTAATTTACA	1-1-2-1-1-7-4-1-2	TtTTaTctatttaATTTaCA	774_1	-19.84	30680
  774	TTTTATCTATTTAATTTACA	2-1-1-1-2-6-3-1-3	TTtTaTCtatttaATTTACA	774_2	-20.79	30680
  774	TTTTATCTATTTAATTTACA	4-2-1-6-2-1-4	TTTTatCtatttaATtTACA	774_3	-21.94	30680
  774	TTTTATCTATTTAATTTACA	1-1-5-6-2-3-2	TtTTATCtatttaATttaCA	774_4	-21.32	30680
  774	TTTTATCTATTTAATTTACA	2-2-3-6-1-2-4	TTttATCtatttaAttTACA	774_5	-20.67	30680
  775	CTTTTATCTATTTAATTTA	5-7-4-1-2	CTTTTatctattTAATtTA	775_1	-21.18	30682
  775	CTTTTATCTATTTAATTTA	5-7-2-1-4	CTTTTatctattTAaTTTA	775_2	-21.18	30682
  775	CTTTTATCTATTTAATTTA	5-7-2-2-3	CTTTTatctattTAatTTA	775_3	-20.23	30682
  775	CTTTTATCTATTTAATTTA	3-1-1-7-1-1-5	CTTtTatctattTaATTTA	775_4	-19.83	30682
  775	CTTTTATCTATTTAATTTA	2-1-2-7-1-1-1-1-3	CTtTTatctattTaAtTTA	775_5	-18.07	30682
  776	CTTTTATCTATTTAATTTAC	1-1-5-6-4-1-2	CtTTTATctatttAATTTAC	776_1	-21.25	30681
  776	CTTTTATCTATTTAATTTAC	3-1-1-8-3-1-3	CTTtTatctatttAATtTAC	776_2	-20.13	30681
  776	CTTTTATCTATTTAATTTAC	5-8-2-1-4	CTTTTatctatttAAtTTAC	776_3	-21.02	30681
  776	CTTTTATCTATTTAATTTAC	1-1-2-1-2-6-2-1-4	CtTTTATctatttAAtTTAC	776_4	-19.49	30681
  776	CTTTTATCTATTTAATTTAC	2-1-4-6-2-2-3	CTtTTATctatttAAttTAC	776_5	-21.33	30681
  777	ACTTTTATCTATTTAATTT	4-1-1-6-4-1-2	ACTTtTatctatTTAAtTT	777_1	-20.04	30683
  777	ACTTTTATCTATTTAATTT	3-1-2-6-3-1-3	ACTtTTatctatTTAaTTT	777_2	-20.48	30683
  777	ACTTTTATCTATTTAATTT	5-7-2-1-4	ACTTTtatctatTTaATTT	777_3	-20.54	30683
  777	ACTTTTATCTATTTAATTT	2-2-2-6-2-1-4	ACttTTatctatTTaATTT	777_4	-19.26	30683
  777	ACTTTTATCTATTTAATTT	4-1-1-6-1-2-4	ACTTtTatctatTtaATTT	777_5	-19.21	30683
  778	ACTTTTATCTATTTAATTTA	2-3-1-7-4-1-2	ACtttTatctattTAATtTA	778_1	-19.89	30682
  778	ACTTTTATCTATTTAATTTA	1-1-4-7-2-1-1-1-2	AcTTTTatctattTAaTtTA	778_2	-19.82	30682
  778	ACTTTTATCTATTTAATTTA	3-2-1-7-2-2-3	ACTttTatctattTAatTTA	778_3	-20.13	30682
  778	ACTTTTATCTATTTAATTTA	4-9-1-1-5	ACTTttatctattTaATTTA	778_4	-21.14	30682
  778	ACTTTTATCTATTTAATTTA	2-1-3-7-1-1-5	ACtTTTatctattTaATTTA	778_5	-21.49	30682
  779	ACTTTTATCTATTTAATT	2-1-3-6-2-1-3	ACtTTTatctatTTaATT	779_1	-18.25	30684
  779	ACTTTTATCTATTTAATT	4-1-1-7-5	ACTTtTatctattTAATT	779_2	-19.17	30684
  779	ACTTTTATCTATTTAATT	3-1-2-7-5	ACTtTTatctattTAATT	779_3	-19.17	30684
  779	ACTTTTATCTATTTAATT	2-1-3-7-5	ACtTTTatctattTAATT	779_4	-18.79	30684
  779	ACTTTTATCTATTTAATT	1-1-4-7-5	AcTTTTatctattTAATT	779_5	-18.42	30684
  780	AACTTTTATCTATTTAATT	5-7-3-1-3	AACTTttatctaTTTaATT	780_1	-19.61	30684
  780	AACTTTTATCTATTTAATT	5-8-3-1-2	AACTTttatctatTTAaTT	780_2	-18.68	30684
  780	AACTTTTATCTATTTAATT	4-1-1-7-3-1-2	AACTtTtatctatTTAaTT	780_3	-18.17	30684
  780	AACTTTTATCTATTTAATT	1-1-4-7-2-1-3	AaCTTTtatctatTTaATT	780_4	-18.45	30684
  780	AACTTTTATCTATTTAATT	5-9-5	AACTTttatctattTAATT	780_5	-19.19	30684
  781	AACTTTTATCTATTTAAT	5-8-5	AACTTttatctatTTAAT	781_1	-18.18	30685
  782	AACTTTTATCTATTTAATTT	1-1-1-1-3-6-4-1-2	AaCtTTTatctatTTAAtTT	782_1	-19.40	30683
  782	AACTTTTATCTATTTAATTT	4-2-1-6-3-1-3	AACTttTatctatTTAaTTT	782_2	-20.41	30683
  782	AACTTTTATCTATTTAATTT	5-1-1-6-2-1-4	AACTTtTatctatTTaATTT	782_3	-21.20	30683
  782	AACTTTTATCTATTTAATTT	2-1-4-6-1-2-4	AAcTTTTatctatTtaATTT	782_4	-19.21	30683
  782	AACTTTTATCTATTTAATTT	1-1-2-1-2-7-2-1-3	AaCTtTTatctattTAaTTT	782_5	-19.40	30683
  783	TAACTTTTATCTATTTAAT	2-1-3-6-4-1-2	TAaCTTttatctATTTaAT	783_1	-19.91	30685
  783	TAACTTTTATCTATTTAAT	2-1-3-6-2-1-4	TAaCTTttatctATtTAAT	783_2	-19.93	30685
  783	TAACTTTTATCTATTTAAT	5-7-2-1-1-1-2	TAACTtttatctATtTaAT	783_3	-18.79	30685
  783	TAACTTTTATCTATTTAAT	1-1-4-6-1-1-5	TaACTTttatctAtTTAAT	783_4	-19.16	30685
  783	TAACTTTTATCTATTTAAT	5-9-5	TAACTtttatctatTTAAT	783_5	-19.60	30685
  784	TAACTTTTATCTATTTAATT	4-1-1-7-1-1-2-1-2	TAACtTttatctaTtTAaTT	784_1	-18.83	30684
  784	TAACTTTTATCTATTTAATT	2-1-4-7-3-1-2	TAaCTTTtatctatTTAaTT	784_2	-20.71	30684
  784	TAACTTTTATCTATTTAATT	2-1-3-8-2-1-3	TAaCTTttatctatTTaATT	784_3	-19.87	30684
  784	TAACTTTTATCTATTTAATT	1-1-5-7-2-1-3	TaACTTTtatctatTTaATT	784_4	-20.35	30684
  784	TAACTTTTATCTATTTAATT	5-10-5	TAACTtttatctattTAATT	784_5	-20.61	30684
  785	TAACTTTTATCTATTTAA	5-7-2-1-3	TAACTtttatctATtTAA	785_1	-18.07	30686
  786	ATAACTTTTATCTATTTAA	3-1-2-6-4-1-2	ATAaCTtttatcTATTtAA	786_1	-20.14	30686
  786	ATAACTTTTATCTATTTAA	4-1-1-6-3-1-3	ATAAcTtttatcTATtTAA	786_2	-20.03	30686
  786	ATAACTTTTATCTATTTAA	2-1-3-6-2-1-4	ATaACTtttatcTAtTTAA	786_3	-20.33	30686
  786	ATAACTTTTATCTATTTAA	3-1-2-6-2-2-3	ATAaCTtttatcTAttTAA	786_4	-19.84	30686
  786	ATAACTTTTATCTATTTAA	5-7-1-1-5	ATAACttttatcTaTTTAA	786_5	-20.30	30686
  787	ATAACTTTTATCTATTTAAT	3-1-3-6-3-2-2	ATAaCTTttatctATTtaAT	787_1	-20.73	30685
  787	ATAACTTTTATCTATTTAAT	2-1-4-6-2-1-4	ATaACTTttatctATtTAAT	787_2	-21.66	30685
  787	ATAACTTTTATCTATTTAAT	3-1-2-7-1-2-4	ATAaCTtttatctAttTAAT	787_3	-19.93	30685
  787	ATAACTTTTATCTATTTAAT	4-2-1-7-3-1-2	ATAActTttatctaTTTaAT	787_4	-18.98	30685
  787	ATAACTTTTATCTATTTAAT	2-1-4-8-5	ATaACTTttatctatTTAAT	787_5	-21.13	30685
  788	TATAACTTTTATCTATTTA	1-1-2-1-1-6-4-1-2	TaTAaCttttatCTATtTA	788_1	-21.10	30687
  788	TATAACTTTTATCTATTTA	2-2-2-6-3-1-3	TAtaACttttatCTAtTTA	788_2	-20.60	30687
  788	TATAACTTTTATCTATTTA	3-1-2-6-2-1-4	TATaACttttatCTaTTTA	788_3	-22.09	30687
  788	TATAACTTTTATCTATTTA	5-7-1-1-5	TATAActtttatCtATTTA	788_4	-21.33	30687
  788	TATAACTTTTATCTATTTA	4-1-1-7-2-2-2	TATAaCttttatcTAttTA	788_5	-20.13	30687
  789	TATAACTTTTATCTATTTAA	4-1-1-7-4-1-2	TATAaCttttatcTATTTAA	789_1	-21.18	30686
  789	TATAACTTTTATCTATTTAA	2-2-3-6-3-1-3	TAtaACTtttatcTATtTAA	789_2	-21.32	30686
  789	TATAACTTTTATCTATTTAA	1-1-5-6-2-1-4	TaTAACTtttatcTAtTTAA	789_3	-21.97	30686
  789	TATAACTTTTATCTATTTAA	3-1-2-7-1-1-1-1-3	TATaACttttatcTaTtTAA	789_4	-19.86	30686
  789	TATAACTTTTATCTATTTAA	4-2-1-6-1-2-4	TATAacTtttatcTatTTAA	789_5	-20.09	30686
  790	TTATAACTTTTATCTATTT	2-1-3-6-4-1-2	TTaTAActtttaTCTAtTT	790_1	-21.00	30688
  790	TTATAACTTTTATCTATTT	5-7-2-2-3	TTATAacttttaTCtaTTT	790_2	-20.52	30688
  790	TTATAACTTTTATCTATTT	4-1-1-6-1-1-5	TTATaActtttaTcTATTT	790_3	-21.08	30688
  790	TTATAACTTTTATCTATTT	4-1-1-7-3-1-2	TTATaActtttatCTAtTT	790_4	-20.46	30688
  790	TTATAACTTTTATCTATTT	2-1-3-8-5	TTaTAActtttatcTATTT	790_5	-19.98	30688
  791	TTATAACTTTTATCTATT	5-7-3-1-2	TTATAacttttaTCTaTT	791_1	-20.32	30689
  791	TTATAACTTTTATCTATT	5-7-1-1-4	TTATAacttttaTcTATT	791_2	-19.99	30689
  791	TTATAACTTTTATCTATT	4-1-1-7-5	TTATaActtttatCTATT	791_3	-20.40	30689
  791	TTATAACTTTTATCTATT	4-9-5	TTATaacttttatCTATT	791_4	-19.98	30689
  791	TTATAACTTTTATCTATT	2-1-3-7-5	TTaTAActtttatCTATT	791_5	-19.81	30689
  792	TTATAACTTTTATCTATTTA	1-2-1-1-2-6-3-2-2	TtaTaACttttatCTAttTA	792_1	-20.10	30687
  792	TTATAACTTTTATCTATTTA	3-2-1-7-1-1-2-1-2	TTAtaActtttatCtATtTA	792_2	-18.80	30687
  792	TTATAACTTTTATCTATTTA	4-1-2-6-1-3-3	TTATaACttttatCtatTTA	792_3	-21.34	30687
  792	TTATAACTTTTATCTATTTA	2-1-2-1-1-7-2-1-3	TTaTAaCttttatcTAtTTA	792_4	-20.83	30687
  792	TTATAACTTTTATCTATTTA	1-1-4-8-1-1-4	TtATAActtttatcTaTTTA	792_5	-19.94	30687
  793	CTTATAACTTTTATCTATT	1-1-1-1-2-6-3-2-2	CtTaTAacttttATCtaTT	793_1	-19.45	30689
  793	CTTATAACTTTTATCTATT	1-2-3-6-1-1-5	CttATAacttttAtCTATT	793_2	-21.25	30689
  793	CTTATAACTTTTATCTATT	3-2-1-8-5	CTTatAacttttatCTATT	793_3	-20.78	30689
  793	CTTATAACTTTTATCTATT	1-1-3-9-2-1-2	CtTATaacttttatCTaTT	793_4	-19.82	30689
  793	CTTATAACTTTTATCTATT	5-9-1-1-3	CTTATaacttttatCtATT	793_5	-20.81	30689
  794	CTTATAACTTTTATCTAT	5-7-3-1-2	CTTATaacttttATCtAT	794_1	-21.02	30690
  794	CTTATAACTTTTATCTAT	1-1-3-7-1-1-4	CtTATaacttttAtCTAT	794_2	-20.04	30690
  794	CTTATAACTTTTATCTAT	2-2-1-8-5	CTtaTaacttttaTCTAT	794_3	-19.59	30690
  794	CTTATAACTTTTATCTAT	3-1-2-8-4	CTTaTAacttttatCTAT	794_4	-20.86	30690
  794	CTTATAACTTTTATCTAT	5-10-3	CTTATaacttttatcTAT	794_5	-19.99	30690
  795	CTTATAACTTTTATCTATTT	1-1-1-2-2-6-2-1-1-1-2	CtTatAActtttaTCtAtTT	795_1	-18.22	30688
  795	CTTATAACTTTTATCTATTT	1-1-1-1-2-8-2-1-3	CtTaTAacttttatCTaTTT	795_2	-20.86	30688
  795	CTTATAACTTTTATCTATTT	2-1-2-1-1-7-2-2-2	CTtATaActtttatCTatTT	795_3	-20.54	30688
  795	CTTATAACTTTTATCTATTT	3-2-1-8-1-1-1-1-2	CTTatAacttttatCtAtTT	795_4	-18.19	30688
  795	CTTATAACTTTTATCTATTT	1-2-2-1-1-9-4	CttATaActtttatctATTT	795_5	-18.61	30688
  796	CTTATAACTTTTATCTA	5-6-2-1-3	CTTATaactttTAtCTA	796_1	-21.44	30691
  796	CTTATAACTTTTATCTA	5-6-1-2-3	CTTATaactttTatCTA	796_2	-20.31	30691
  796	CTTATAACTTTTATCTA	1-1-3-7-5	CtTATaacttttATCTA	796_3	-19.90	30691
  796	CTTATAACTTTTATCTA	3-1-1-8-4	CTTaTaacttttaTCTA	796_4	-18.77	30691
  796	CTTATAACTTTTATCTA	2-1-2-8-4	CTtATaacttttaTCTA	796_5	-18.43	30691
  797	GCTTATAACTTTTATCTA	2-2-2-6-2-2-2	GCttATaactttTAtcTA	797_1	-21.32	30691
  797	GCTTATAACTTTTATCTA	4-9-1-1-3	GCTTataacttttAtCTA	797_2	-21.88	30691
  797	GCTTATAACTTTTATCTA	2-12-4	GCttataacttttaTCTA	797_3	-20.47	30691
  797	GCTTATAACTTTTATCTA	2-1-1-1-1-9-3	GCtTaTaacttttatCTA	797_4	-20.94	30691
  797	GCTTATAACTTTTATCTA	1-1-4-10-2	GcTTATaacttttatcTA	797_5	-19.62	30691
  798	GCTTATAACTTTTATCT	2-9-1-2-3	GCttataacttTtaTCT	798_1	-18.54	30692
  798	GCTTATAACTTTTATCT	2-10-5	GCttataactttTATCT	798_2	-20.90	30692
  798	GCTTATAACTTTTATCT	4-8-1-1-3	GCTTataactttTaTCT	798_3	-21.40	30692
  798	GCTTATAACTTTTATCT	2-1-2-8-4	GCtTAtaacttttATCT	798_4	-21.00	30692
  798	GCTTATAACTTTTATCT	5-10-2	GCTTAtaacttttatCT	798_5	-20.68	30692
  799	TGCTTATAACTTTTATC	3-8-3-1-2	TGCttataactTTTaTC	799_1	-19.59	30693
  799	TGCTTATAACTTTTATC	3-8-2-1-3	TGCttataactTTTATC	799_2	-19.26	30693
  799	TGCTTATAACTTTTATC	2-10-5	TGcttataacttTTATC	799_3	-18.08	30693
  799	TGCTTATAACTTTTATC	5-8-4	TGCTTataactttTATC	799_4	-22.34	30693
  799	TGCTTATAACTTTTATC	3-10-4	TGCttataactttTATC	799_5	-19.90	30693
  800	TGCTTATAACTTTTATCT	3-9-3-1-2	TGCttataacttTTAtCT	800_1	-22.27	30692
  800	TGCTTATAACTTTTATCT	2-2-2-7-5	TGctTAtaactttTATCT	800_2	-22.61	30692
  800	TGCTTATAACTTTTATCT	3-10-1-1-3	TGCttataactttTaTCT	800_3	-21.45	30692
  800	TGCTTATAACTTTTATCT	1-1-1-1-2-8-4	TgCtTAtaacttttATCT	800_4	-20.79	30692
  800	TGCTTATAACTTTTATCT	4-1-1-10-2	TGCTtAtaacttttatCT	800_5	-20.89	30692
  801	CTGCTTATAACTTTTATC	2-1-1-8-2-1-3	CTgCttataactTTtATC	801_1	-20.05	30693
  801	CTGCTTATAACTTTTATC	4-8-1-3-2	CTGCttataactTttaTC	801_2	-21.02	30693
  801	CTGCTTATAACTTTTATC	2-1-1-10-4	CTgCttataactttTATC	801_3	-20.69	30693
  801	CTGCTTATAACTTTTATC	1-1-2-10-1-1-2	CtGCttataactttTaTC	801_4	-18.86	30693
  801	CTGCTTATAACTTTTATC	1-1-4-9-3	CtGCTTataacttttATC	801_5	-21.47	30693
  802	CTCTGCTTATAACTTTT	1-1-1-1-1-6-2-1-3	CtCtGcttataACtTTT	802_1	-18.92	30696
  802	CTCTGCTTATAACTTTT	1-1-1-1-1-7-2-1-2	CtCtGcttataaCTtTT	802_2	-18.47	30696
  802	CTCTGCTTATAACTTTT	1-1-2-8-1-1-3	CtCTgcttataaCtTTT	802_3	-19.44	30696
  802	CTCTGCTTATAACTTTT	1-2-2-7-1-1-3	CtcTGcttataaCtTTT	802_4	-19.02	30696
  802	CTCTGCTTATAACTTTT	3-1-1-10-2	CTCtGcttataacttTT	802_5	-18.16	30696
  803	CCTCTGCTTATAACTTT	1-1-2-7-2-1-3	CcTCtgcttatAAcTTT	803_1	-20.60	30697
  803	CCTCTGCTTATAACTTT	2-9-1-3-2	CCtctgcttatAactTT	803_2	-19.28	30697
  803	CCTCTGCTTATAACTTT	2-2-1-7-1-2-2	CCtcTgcttataActTT	803_3	-20.58	30697
  803	CCTCTGCTTATAACTTT	1-2-1-8-1-2-2	CctCtgcttataActTT	803_4	-18.06	30697
  803	CCTCTGCTTATAACTTT	2-1-1-9-1-1-2	CCtCtgcttataaCtTT	803_5	-21.12	30697
  804	CTACTATACTTTCCTCT	3-8-2-2-2	CTActatacttTCctCT	804_1	-22.54	30709
  804	CTACTATACTTTCCTCT	1-1-1-9-2-1-2	CtActatactttCCtCT	804_2	-21.39	30709
  804	CTACTATACTTTCCTCT	1-2-1-8-1-2-2	CtaCtatactttCctCT	804_3	-19.70	30709
  804	CTACTATACTTTCCTCT	2-11-1-1-2	CTactatactttcCtCT	804_4	-20.45	30709
  804	CTACTATACTTTCCTCT	1-3-1-8-1-1-2	CtacTatactttcCtCT	804_5	-19.77	30709
  805	TCTACTATACTTTCCTCT	2-1-1-9-1-2-2	TCtActatactttCctCT	805_1	-21.40	30709
  805	TCTACTATACTTTCCTCT	2-2-1-8-1-2-2	TCtaCtatactttCctCT	805_2	-22.20	30709
  805	TCTACTATACTTTCCTCT	2-11-1-2-2	TCtactatactttCctCT	805_3	-21.20	30709
  805	TCTACTATACTTTCCTCT	2-1-1-10-1-1-2	TCtActatactttcCtCT	805_4	-21.52	30709
  805	TCTACTATACTTTCCTCT	2-2-1-9-1-1-2	TCtaCtatactttcCtCT	805_5	-22.32	30709
  806	TTCTACTATACTTTCCT	1-1-1-8-1-3-2	TtCtactatacTttcCT	806_1	-18.06	30711
  806	TTCTACTATACTTTCCT	1-2-1-7-1-3-2	TtcTactatacTttcCT	806_2	-18.02	30711
  806	TTCTACTATACTTTCCT	1-1-1-1-1-7-1-1-3	TtCtActatactTtCCT	806_3	-20.41	30711
  806	TTCTACTATACTTTCCT	1-1-1-10-4	TtCtactatacttTCCT	806_4	-20.90	30711
  806	TTCTACTATACTTTCCT	1-1-1-1-1-9-3	TtCtActatactttCCT	806_5	-20.11	30711
  807	TTCTACTATACTTTCCTC	1-2-1-8-1-1-1-1-2	TtcTactatactTtCcTC	807_1	-19.51	30710
  807	TTCTACTATACTTTCCTC	1-1-1-2-1-6-1-3-2	TtCtaCtatactTtccTC	807_2	-19.77	30710
  807	TTCTACTATACTTTCCTC	1-1-1-1-1-9-1-1-2	TtCtActatactttCcTC	807_3	-19.44	30710
  807	TTCTACTATACTTTCCTC	1-1-1-12-3	TtCtactatactttcCTC	807_4	-20.04	30710
  807	TTCTACTATACTTTCCTC	1-2-1-1-1-10-2	TtcTaCtatactttccTC	807_5	-19.43	30710
  808	TTTCCATCTACTATTAAT	1-1-3-7-3-1-2	TtTCCatctactATTaAT	808_1	-21.43	39804
  808	TTTCCATCTACTATTAAT	2-1-2-7-1-1-1-1-2	TTtCCatctactAtTaAT	808_2	-19.50	39804
  808	TTTCCATCTACTATTAAT	1-1-4-6-1-2-3	TtTCCAtctactAttAAT	808_3	-20.72	39804
  808	TTTCCATCTACTATTAAT	2-1-2-8-1-1-3	TTtCCatctactaTtAAT	808_4	-19.43	39804
  808	TTTCCATCTACTATTAAT	4-1-1-8-4	TTTCcAtctactatTAAT	808_5	-20.12	39804
  809	TTTCCATCTACTATTAA	5-6-3-1-2	TTTCCatctacTATtAA	809_1	-21.74	39805
  809	TTTCCATCTACTATTAA	2-1-2-6-2-1-3	TTtCCatctacTAtTAA	809_2	-20.76	39805
  809	TTTCCATCTACTATTAA	1-1-3-6-1-1-4	TtTCCatctacTaTTAA	809_3	-20.75	39805
  809	TTTCCATCTACTATTAA	2-1-2-7-5	TTtCCatctactATTAA	809_4	-20.54	39805
  809	TTTCCATCTACTATTAA	5-9-3	TTTCCatctactatTAA	809_5	-20.18	39805
  810	GTTTCCATCTACTATTA	3-9-2-1-2	GTTtccatctacTAtTA	810_1	-20.81	39806
  810	GTTTCCATCTACTATTA	1-1-1-1-1-7-1-1-3	GtTtCcatctacTaTTA	810_2	-19.35	39806
  810	GTTTCCATCTACTATTA	2-2-1-7-1-2-2	GTttCcatctacTatTA	810_3	-19.64	39806
  810	GTTTCCATCTACTATTA	3-1-1-8-4	GTTtCcatctactATTA	810_4	-21.37	39806
  810	GTTTCCATCTACTATTA	1-2-2-10-2	GttTCcatctactatTA	810_5	-18.14	39806
  811	AATACAAAATCATCTTAC	3-1-2-6-1-1-4	AATaCAaaatcaTcTTAC	811_1	-18.05	39836
  811	AATACAAAATCATCTTAC	4-9-5	AATAcaaaatcatCTTAC	811_2	-18.25	39836
  811	AATACAAAATCATCTTAC	3-1-2-7-5	AATaCAaaatcatCTTAC	811_3	-19.20	39836
  811	AATACAAAATCATCTTAC	2-1-3-7-5	AAtACAaaatcatCTTAC	811_4	-18.12	39836
  811	AATACAAAATCATCTTAC	1-1-4-7-5	AaTACAaaatcatCTTAC	811_5	-19.50	39836
  812	AATACAAAATCATCTTACA	2-2-2-6-4-1-2	AAtaCAaaatcaTCTTaCA	812_1	-20.31	39835
  812	AATACAAAATCATCTTACA	4-8-3-2-2	AATAcaaaatcaTCTtaCA	812_2	-19.80	39835
  812	AATACAAAATCATCTTACA	3-1-2-6-2-1-4	AATaCAaaatcaTCtTACA	812_3	-21.91	39835
  812	AATACAAAATCATCTTACA	1-1-4-7-2-2-2	AaTACAaaatcatCTtaCA	812_4	-19.93	39835
  812	AATACAAAATCATCTTACA	5-8-1-1-4	AATACaaaatcatCtTACA	812_5	-20.93	39835
  813	TAATACAAAATCATCTTA	1-1-4-6-3-1-2	TaATACaaaatcATCtTA	813_1	-18.46	39837
  813	TAATACAAAATCATCTTA	5-8-5	TAATAcaaaatcaTCTTA	813_2	-19.57	39837
  813	TAATACAAAATCATCTTA	5-9-4	TAATAcaaaatcatCTTA	813_3	-18.44	39837
  813	TAATACAAAATCATCTTA	2-1-3-8-4	TAaTACaaaatcatCTTA	813_4	-18.20	39837
  813	TAATACAAAATCATCTTA	1-1-4-8-4	TaATACaaaatcatCTTA	813_5	-18.18	39837
  814	TAATACAAAATCATCTTAC	2-1-3-6-4-1-2	TAaTACaaaatcATCTtAC	814_1	-19.95	39836
  814	TAATACAAAATCATCTTAC	4-1-1-6-3-1-3	TAATaCaaaatcATCtTAC	814_2	-20.22	39836
  814	TAATACAAAATCATCTTAC	1-2-3-6-1-1-5	TaaTACaaaatcAtCTTAC	814_3	-19.14	39836
  814	TAATACAAAATCATCTTAC	5-8-2-1-3	TAATAcaaaatcaTCtTAC	814_4	-19.90	39836
  814	TAATACAAAATCATCTTAC	4-1-1-8-5	TAATaCaaaatcatCTTAC	814_5	-19.94	39836
  815	TAATACAAAATCATCTTACA	3-2-2-6-2-1-1-1-2	TAAtaCAaaatcaTCtTaCA	815_1	-20.84	39835
  815	TAATACAAAATCATCTTACA	2-3-1-8-2-1-3	TAataCaaaatcatCTtACA	815_2	-18.77	39835
  815	TAATACAAAATCATCTTACA	2-1-2-1-1-7-2-2-2	TAaTAcAaaatcatCTtaCA	815_3	-19.66	39835
  815	TAATACAAAATCATCTTACA	1-1-1-1-2-8-1-1-4	TaAtACaaaatcatCtTACA	815_4	-19.11	39835
  815	TAATACAAAATCATCTTACA	4-10-1-1-1-1-2	TAATacaaaatcatCtTaCA	815_5	-19.22	39835
  816	TCTGTATACACCATCCCA	2-10-1-1-1-1-2	TCtgtatacaccAtCcCA	816_1	-24.49	46389
  816	TCTGTATACACCATCCCA	2-3-1-6-1-3-2	TCtgtAtacaccAtccCA	816_2	-23.81	46389
  816	TCTGTATACACCATCCCA	2-10-1-3-2	TCtgtatacaccAtccCA	816_3	-23.72	46389
  816	TCTGTATACACCATCCCA	2-1-1-10-1-1-2	TCtGtatacaccatCcCA	816_4	-24.75	46389
  816	TCTGTATACACCATCCCA	2-3-1-8-1-1-2	TCtgtAtacaccatCcCA	816_5	-24.53	46389
  816	TCTGTATACACCATCCCA	2-3-1-10-2	TCtgtAtacaccatccCA	816_6	-23.76	46389
  817	TTCTGACTCCCTATCCA	1-1-1-12-2	TtCtgactccctatcCA	817_1	-22.56	46417
  818	TTTCTGACTCCCTATCC	1-2-1-11-2	TttCtgactccctatCC	818_1	-22.64	46418

• Designs refer to the gapmer design, F-G-F′, where each number represents the number of consecutive modified nucleosides, e.g 2′ modified nucleosides (first number=5′ flank), followed by the number of DNA nucleosides (second number=gap region), followed by the number of modified nucleosides, e.g 2′ modified nucleosides (third number=3′ flank), optionally preceded by or followed by further repeated regions of DNA and LNA, which are not necessarily part of the contiguous sequence that is complementary to the target nucleic acid. For some oligonucleotides in table 3 the flanks are mixed flanks, such flanks start and end with a 2′ modified nucleosides, in these cases the gap region is the number above 5 not located at the 5′ or 3′ terminal in of the design.
• For the oligonucleotide compounds capital letters represent beta-D-oxy LNA nucleosides, lowercase letters represent DNA nucleosides, all LNA C are 5-methyl cytosine, and 5-methyl DNA cytosines are presented by “e”, all internucleoside linkages are phosphorothioate internucleoside linkages.
• Oligonucleotides with an EX-EX indication as Start on SEQ ID NO: 1 are exon-exon spanning oligonucleotides designed to be complementary across exon-exon junctions of SNHG14-023 (ENST00000554726). The oligonucleotides primarily span exon2 and exon3 (i.e. are complementary to a region in exon2 and a region in exon 3)
Oligonucleotide Synthesis
• Oligonucleotide synthesis is generally known in the art. Below is a protocol which may be applied. The oligonucleotides of the present invention may have been produced by slightly varying methods in terms of apparatus, support and concentrations used.
• Oligonucleotides are synthesized on uridine universal supports using the phosphoramidite approach on a MerMade12 or an Oligomaker DNA/RNA synthesizer at 1-4 μmol scale. At the end of the synthesis, the oligonucleotides are cleaved from the solid support using aqueous ammonia for 5-16 hours at 60° C. The oligonucleotides are purified by reverse phase HPLC (RP-HPLC) or by solid phase extractions and characterized by UPLC, and the molecular mass is further confirmed by ESI-MS.
Elongation of the Oligonucleotide:
• The coupling of β-cyanoethyl-phosphoramidites (DNA-A(Bz), DNA-G(ibu), DNA-C(Bz), DNA-T, LNA-5-methyl-C(Bz), LNA-A(Bz), LNA-G(dmf), LNA-T or amino-C6 linker) is performed by using a solution of 0.1 M of the 5′-O-DMT-protected amidite in acetonitrile and DCI (4,5-dicyanoimidazole) in acetonitrile (0.25 M) as activator. For the final cycle a phosphoramidite with desired modifications can be used, e.g. a C6 linker for attaching a conjugate group or a conjugate group as such. Thiolation for introduction of phosphorthioate linkages is carried out by using xanthane hydride (0.01 M in acetonitrile/pyridine 9:1). Phosphordiester linkages can be introduced using 0.02 M iodine in THF/Pyridine/water 7:2:1. The rest of the reagents are the ones typically used for oligonucleotide synthesis.
Purification by RP-HPLC:
• The crude compounds are purified by preparative RP-HPLC on a Phenomenex Jupiter C18 10μ 150×10 mm column. 0.1 M ammonium acetate pH 8 and acetonitrile is used as buffers at a flow rate of 5 mL/min. The collected fractions are lyophilized to give the purified compound typically as a white solid.
Abbreviations DCI: 4,5-Dicyanoimidazole DCM: Dichloromethane DMF: Dimethylformamide DMT: 4,4′-Dimethoxytrityl THF: Tetrahydrofurane Bz: Benzoyl Ibu: Isobutyryl
• RP-HPLC: Reverse phase high performance liquid chromatography
T_m Assay
• Oligonucleotide and RNA target duplexes are diluted to 3 mM in 500 ml RNase-free water and mixed with 500 ml 2×T_m-buffer (200 mM NaCl, 0.2 mM EDTA, 20 mM Naphosphate, pH 7.0). The solution is heated to 95° C. for 3 min and then allowed to anneal in room temperature for 30 min. The duplex melting temperatures (T_m) is measured on a Lambda 40 UV/VIS Spectrophotometer equipped with a Peltier temperature programmer PTP6 using PE Templab software (Perkin Elmer). The temperature is ramped up from 20° C. to 95° C. and then down to 25° C., recording absorption at 260 nm. First derivative and the local maximums of both the melting and annealing are used to assess the duplex T_m.
Preparation of Mouse Primary Cortical Neuron Cell Cultures
• Primary cortical neuron cultures were prepared from mouse embryo brains of 15 days of age according to standard procedure. In brief, culture plates were coated with Poly-L-Lysine (50 μg/ml Poly-L-Lysine, 10 mM Na-tetraborate, pH 8 buffer) for 2-3 hrs at room temperature. The plates were washed with 1×PBS before use. Harvested mouse embryo brains were dissected and homogenized by a razor blade and submerged into 38 ml dissection medium (HBSS, 0.01 M Hepes, Penicillin/Streptomycin). Then, 2 ml trypsin was added and cells were incubated for 30 min at 37° C. and centrifuged down. The cells were dissolved in 20 ml DMEM (+10% FBS) and passed through a syringe for further homogenization. This was followed by centrifugation at 500 rpm for 15 mins. The cells were dissolved in DMEM (+10% FBS) and seeded in 96 well plates (0.1× 10̂6 cells/well in 100 μl). The neuronal cell cultures were ready for use directly after seeding.
Screening Oligonucleotides in Mouse Primary Cortical Neuron Cell Cultures
• Cells were cultured in growth medium (Gibco Neurobasal medium, B27 supplement, Glutamax, Pencillin-streptomycin) in 96-well plates and incubated with oligonucleotides for 3 days at the desired concentrations. Total RNA was isolated from the cells and the knock-down efficacy was measured by qPCR analysis using the qScript™ XLT One-Step RT-qPCR ToughMix®, Low ROX™ kit from Quanta Bioscience (95134-500). A commercial taqman assays from Thermo Fisher Scientific was used to measure Ube3a_ATS including GAPDH for normalization.
Generation of Human Primary Neuronal Cell Cultures
• Any cell lines at any described time point was incubated at 37° C., 5% CO2 concentration and 95% relative humidity.
• Human Induced Pluripotent Stem Cells (hiPSC) Culture
• Whole human blood samples were obtained from patients diagnosed with Angelman syndrome. The subsequent cultures of primary Peripheral Blood Mononuclear Cells (PMCSs) were enriched for erythroblasts. Patient-specific iPSC lines were generated by reprogramming erythroblast with CytoTune-iPS Sendai Reprogramming Kit (Thermo Fisher Scientific). Derived iPSC lines were maintained in feeder-free conditions using hESC-qualified Matrigel (Corning) in mTESR1 (STEMCELL Technologies) with daily medium replacement. Upon reaching confluence, colonies were dissociated into cell cluster of 50-200 μm in size using Gentle Cell Dissociation Reagent (STEMCELL Technologies) and subcultured at a ratio of 1:10-1:20 in the presence of 10 μM Y-27632 (Calbiochem).
• Differentiation into Neural Progenitor Cells (NPC)
• Upon induction of neural differentiation iPSC-derived cells were maintained in basal medium composed of equal volumes of DMEM:F12 Glutamax medium and Neurobasal medium (Gibco, Invitrogen), supplemented with 1×B27 (Gibco, Invitrogen), 1×N2 (Gibco, Invitrogen), 0.1 mM beta-mercaptoethanol (Gibco, Invitrogen) and indicated supplements.
• Neural progenitor cells (NPCs) were derived from hiPSCs by dual SMAD inhibition and according to published procedures with slight modifications (Chambers et al. 2009 Nat Biotechnol. Vol. 3 pp. 275-80, Boissart et al., 2013 Transl Psychiatry. 3:e294). HiPSCs were dissociated with Accutase (Innovative Cell Technologies Inc.) into a single cell suspension and resuspended in basic medium further supplemented with 10 μM Y-27632 (Calbiochem), 5 ng/ml FGF (Peprotech), 10 μM SB-431542 (Calbiochem) and 100 nM LDN (Calbiochem). Single cell suspension was transferred to AggreWell800 plates (STEMCELL Technologies) enabling the formation of aggregates consisting of 8000 cells. After 5 days neural aggregates were transferred onto plates coated with poly-L-ornithine (Sigma) and laminin (Roche) and allowed to form neural rosettes under continued dual SMAD inhibition (SB-431542 and LDN) in basic medium supplemented with FGF. Neural rosettes were selectively isolated using STEMdiff™ Neural Rosette Selection Reagent (STEMCELL Technologies), replated onto dishes coated with poly-L-ornithine and Laminin521 (BioLamina) and expanded in basic medium supplemented with 10 ng/ml FGF (Peprotech), 10 ng/ml EGF (RnD), and 20 ng/ml BDNF (Peprotech). When reaching confluency, cells were enzymatically dissociated with 0.05% Trypsin/EDTA (Gibco, Invitrogen) and sub-cultured. Continued passaging in basic medium supplemented with FGF, EGF and BDNF leads to a stable neural progenitor cell line (NPC line) within 10 to 20 passages. A stable neural progenitor cell line is defined by its capacity to self-renew and by the expression of the developmental stage-specific markers Sox2 and Nestin. Upon specific stimuli, NPCs differentiate into neuronal (MAP2+, Tau+, HuC/D+) and astroglial (GFAP+) progenies (Dunkley et al., 2015 Proteomics Clin Appl. Vol. 7-8 pp. 684-94).
NPC Culture
• Conditions for NPC culture have been described previously and were used with slight modifications (Boissart et al., 2013 Transl Psychiatry. 3:e294). In brief, cells were maintained in dishes coated with Laminin521 (BioLamina) and cultured in basic medium [composed of equal volumes of DMEM:F12 Glutamax medium and Neurobasal medium (Gibco, Invitrogen), supplemented with 1×B27 (Gibco, Invitrogen), 1×N2 (Gibco, Invitrogen), 0.1 mM beta-mercaptoethanol (Gibco, Invitrogen)] and supplemented with 10 ng/ml FGF (Peprotech), 10 ng/ml EGF (RnD), and 20 ng/ml BDNF (Peprotech).
• Differentiation into Neuronal Cell Culture
• To induce neuronal differentiation of NPC, cells were dissociated with 0.05% Trypsin/EDTA (Gibco, Invitrogen) into single cell suspension and seeded onto Laminin521 (BioLamina) coated dishes at a density of 12.000 cells/cm2 and maintained in basic medium supplemented with 200 ng/ml Shh (Peprotech), 100 ng/ml FGF8 (Peprotech), and 100 μM ascorbic acid phosphate (Sigma) for a period of 7 days. Subsequently, cells were replated in basal medium supplemented with 20 ng/ml BDNF (Peprotech), 10 ng/ml GDNF (Peprotech), 0.5 mM cAMP (BIOLOG Life Science), and 100 μM ascorbic acid phosphate (Sigma) at a density of 45000 cells/cm2 and differentiated for a period of 21 days. At day 21 of differentiation, differentiated neuronal cultures were replated onto the screening-compatible plate format. Replating was performed by dissociating the cultures with Accutase (Innovative Cell Technologies Inc.) into a single cell suspension. Cells were seeded at a density of 200.000 cells/cm2 in presence of 10 μM Y-27632 (a cell-permeable, reversible, inhibitor of Rho kinases from Calbiochem) into the 384 well microtiter plates for final oligonucleotides screening assay. Neuronal cultures were further differentiated for additional 7 days in basal medium supplemented with 20 ng/ml BDNF (Peprotech), 10 ng/ml GDNF (Peprotech), 0.5 mM cAMP (BIOLOG Life Science), and 100 μM ascorbic acid phosphate (Sigma). Differentiation medium was exchanged twice per week. After a total differentiation period of 35 days neuronal cell cultures were ready for oligonucleotide treatment.
Screening Oligonucleotides in Human Neuronal Cell Cultures—384 Well System
• For screening, oligonucleotide stocks were pre-diluted to the indicated concentrations with water into 384 well microtiter plates (compound plate). The plate layout served as a treatment template. Two microliter oligonucleotide dilution from each well was transferred from the compound plate to a respective culture plate. All liquid handling was done under sterile conditions in a laminar flow using a semi-automated laboratory robotic system (Beckmancoulter). Neuronal cell cultures were incubated with oligonucleotides for 5 days without media change. Subsequently, neuronal cultures were lysed and processed for qPCR assay with RealTime ready Cell lysis and RNA Virus Master kit (Roche). Liquid handling was performed using a semi-automated laboratory robotic system (Beckmancoulter). Samples were analyzed by a Lightcycler480 real-time PCR system (Roche).
• Activity of the oligonucleotides was assessed by qPCR monitoring transcript abundance of UBE3A using the following primers and probes

• 	UBE3a-Sense:
  	Forward primer:
  	(SEQ ID NO: 837)
  	ATATGTGGAAGCCGGAATCT,
  	Reverse primer:
  	(SEQ ID NO: 838)
  	TCCCAGAACTCCCTAATCAGAA,
  	Internal probe labeled with dye FAM:
  	(SEQ ID NO: 839)
  	ATGACGGTGGCTATACCAGG

• The RT-qPCR was multiplexed with PPIA (peptidylprolyl isomerase A) as housekeeping gene for normalization. PPIA primers and probe labeled with the dye VIC were purchased from Thermo Fisher Scientific (assay ID Hs99999904_m1). Each plate includes a non-targeting oligonucleotide (mock) as negative control (TTGaataagtggaTGT (SEQ ID NO: 846)) and a reference oligonucleotide CMP ID NO: 41_1, resulting in up-regulation of UBE3A mRNA.
• Selectivity of oligonucleotides was verified by counter screening for SNORD115 transcript, which is located upstream of SNORD109B on chromosome 15. Expression of SNORD115 was monitored by qPCR using the following primers and probe

• 	Forward primer:
  	(SEQ ID NO: 840)
  	GGGTCAATGATGAGAACCTTAT,
  	Reverse primer
  	(SEQ ID NO: 841)
  	GGGCCTCAGCGTAATCCTATT,
  	Internal probe labeled with the dye FAM:
  	(SEQ ID NO: 842)
  	TTCTGAAGAGAGGTGATGACTTAAAA

• The RT-qPCR was multiplexed with PPIA (Thermo Fisher Scientific) upon oligonucleotide treatment.
• The reduction of the SNHG14 transcript downstream of SNORD109B (also termed the UBE3A suppressor) was measured by RT-qPCR using the following primers and probe

• 	Forward primer:
  	(SEQ ID NO: 843)
  	ATCCGAGGCATGAATCTCAC,
  	Reverse primer:
  	(SEQ ID NO: 844)
  	CAGGCCAAAACCCTTGATAA,
  	Internal probe labeled with dye FAM:
  	(SEQ ID NO: 845)
  	TTGCTGAGCATTTTTGCATC

• The RT-qPCR was multiplexed with PPIA (Thermo Fisher Scientific).
• Data are presented as average % expression relative to mock across all plates and normalized to the reference oligonucleotide to account for plate to plate variation.
Screening Oligonucleotides in Human Neuronal Cell Cultures—96 Well System
• For screening, oligonucleotide stocks were pre-diluted to the indicated concentrations with water into 96 well microtiter plates (compound plate). The plate layout served as a treatment template. Two microliter oligonucleotide dilution from each well was transferred from the compound plate to a respective culture plate. All liquid handling was done under sterile conditions in a laminar flow using a semi-automated laboratory robotic system (Beckman Coulter). Neuronal cell cultures were incubated with oligonucleotides for 5 days without media change. Subsequently, neuronal cultures were lysed and RNA purified using RNA purification kit Pure Link Pro96 (12173011A) LifeTechnologies. Liquid handling was performed using a semi-automated laboratory robotic system (Beckmancoulter). qPCR analysis of Ube3a and Ube3a-ATS was carried out on a ViiA™ 7 Real-Time PCR System Thermo Fisher Scientific using the qScript™ XLT 1-Step RT-qPCR ToughMix Low ROX, from Quanta (95134-50).
• The following primers and probes were used:

• 	qPCR UBE3a-Sense:
  	Forward primer:
  	(SEQ ID NO: 697)
  	ATATGTGGAAGCCGGAATCT,
  	Reverse primer:
  	(SEQ ID NO: 698)
  	TCCCAGAACTCCCTAATCAGAA,
  	Internal probe labeled with dye FAM:
  	(SEQ ID NO: 699)
  	ATGACGGTGGCTATACCAGG

  
  qPCR SNHG14 transcript downstream of SNORD109B (also termed the UBE3A suppressor): Commercially available primer and probe set from ThermoFisher: Hs01372957_m1. These primers amplifies a 87 bp exon-exon spanning sequence in the Genbank transcript AF400500.1
QPCR GAPDH Transcript:
• Commercially available primer and probe set from Thermofisher: Gene Symbol: with following assay details: RefSeq: NM_002046.3, Probe Exon Location:3, Amplicon Size: 122 bp. Corresponding TaqMan Assay ID: Hs99999905_m1.
• The RT-qPCR for both Ube3a and Ube3a-ATS was multiplexed with GAPDH as housekeeping gene for normalization. Each plate includes a non-targeting oligonucleotide (mock) as negative control (TTGaataagtggaTGT (SEQ ID NO: 846)) and a reference oligonucleotide CMP ID NO: 21_1, resulting in up-regulation of UBE3A mRNA. Moreover panel of oligos not targeting Ub3a or SNHG14 transcript downstream of SNORD109B (also termed the UBE3A suppressor) were included to monitor the assay noise and risk of detecting false positives. These were randomly distributed over the plates.
Control Oligonucleotides:

• 	(SEQ ID NO: 819)
  	CGAaccactgaaCAA
  	(SEQ ID NO: 820)
  	CGAaccactgaacAAA
  	(SEQ ID NO: 821)
  	CGAagtgcacaCG
  	(SEQ ID NO: 822)
  	GCGtaaagagaGGT
  	(SEQ ID NO: 823)
  	GAGAaggcacagaCGG
  	(SEQ ID NO: 824)
  	GCGaagtgcacaCGG
  	(SEQ ID NO: 825)
  	GAGaaggcacagaCGG
  	(SEQ ID NO: 826)
  	CGAaccactgAACA
  	(SEQ ID NO: 827)
  	GAAccactgaacAAA
  	(SEQ ID NO: 828)
  	caGCGtaaagagaGG
  	(SEQ ID NO: 829)
  	GCgtaaagagAGG
  	(SEQ ID NO: 830)
  	CGAaccactgaAC
  	(SEQ ID NO: 831)
  	CGAAccactgaaCAAA
  	(SEQ ID NO: 832)
  	AGCgaagtgcacaCGG
  	(SEQ ID NO: 833)
  	AGGtgaagcgaAGTG
  	(SEQ ID NO: 834)
  	TAGTaaactgagCCA
  	(SEQ ID NO: 835)
  	AGAaggcacagaCGG
  	(SEQ ID NO: 836)
  	CCGcagtatggaTCG

Example 1—Oligonucleotide Activity in Mouse Primary Neuronal Cell Cultures
• Oligonucleotides targeting the part of SNHG14 long non-coding RNA which is antisense to the UBE3A pre-mRNA (position 55319 to 141053 of SEQ ID NO: 1) were tested for their ability to reduce the SNHG14 long non-coding RNA transcript preventing UBE3A expression (also termed UBE3A suppressor or UBE3A-SUP in the data table) and their ability to induce UBE3A mRNA re-expression in mouse primary cortical neuron cell cultures, obtained as described in the “Materials and methods” section above. The oligonucleotide concentration was 5 microM.
• The oligonucleotides were screened according to the protocol for screening in mouse cortical neuron cell cultures described in the section “Materials and methods”. The results are shown in table 4.

• TABLE 4
  Oligonucleotide activity in primary
  mouse neuronal cell cultures.

  CMP		% of Mock		% of Mock
  ID NO	oligonucleotide	UBE3A_SUP	sd	UBE3A	sd

  95_1	CTCAtacttgctttaAT	3.6	0.1	154.1	15.1
  95_2	CTcatacttgctttaAT	15.9	2.6	119.8	12.4
  96_1	ACatctcatacttGCTT	4.0	0.5	149.9	11.5
  96_2	ACatctcatacttgcTT	9.3	3.9	139.9	36.4
  96_3	ACatctcatacttgCTT	3.1	0.2	143.2	3.9
  97_1	ACatctcatactTGCT	4.0	1.5	154.5	10.0
  97_2	ACatctcatacttgCT	6.1	1.7	141.1	14.1
  97_3	ACatctcatacttGCT	3.7	0.6	162.7	15.0
  97_4	ACATctcatacttgCT	5.2	0.4	156.7	24.4
  98_1	TAcatctcatactTGCT	5.0	0.9	159.0	15.6
  98_2	TAcatctcatacttgCT	15.5	5.3	130.4	3.4
  98_3	TACAtctcatacttgCT	4.7	0.4	140.3	38.2
  101_1	TACatctcatactTGC	2.6	0.5	152.6	10.2
  101_2	TAcatctcatacttGC	19.2	6.0	112.0	15.0
  101_3	TAcatctcatactTGC	3.5	0.4	117.2	13.7
  101_4	TACAtctcatacttGC	3.0	0.7	140.5	12.4
  100_1	CTAcatctcatactTGC	5.4	0.8	160.4	4.1
  100_2	CTacatctcatacttGC	9.6	3.7	159.2	14.5
  100_3	CTacatctcatactTGC	3.0	0.1	133.2	5.9
  99_2	CCtacatctcatacttGC	7.8	1.4	150.7	11.0
  99_3	CCtacatctcatactTGC	3.2	0.6	134.7	12.5
  99_4	CCtacatctcatacTTGC	2.7	0.2	145.2	4.7
  102_1	CCTAcatctcatactTG	5.8	1.7	127.0	24.5
  102_2	CCtacatctcatactTG	20.2	6.6	129.7	9.2
  102_4	CCTacatctcatacTTG	4.0	0.6	140.2	7.2
  102_3	CCTacatctcatactTG	3.9	1.0	133.3	10.0
  104_1	CCTacatctcataCTT	6.6	1.5	136.5	8.7
  104_3	CCtacatctcatACTT	3.5	0.4	131.4	6.0
  103_1	ACCtacatctcataCTT	5.8	1.4	130.8	0.7
  103_2	ACctacatctcatacTT	11.4	2.2	123.6	12.4
  103_3	ACctacatctcatACTT	5.8	0.8	132.2	4.5
  105_1	TACCtacatctcatacTT	5.2	0.8	152.3	7.2
  106_1	TTAcctacatctcataCTT	13.3	3.0	140.1	17.5
  106_2	TTacctacatctcatacTT	21.0	1.4	116.9	15.0
  107_1	ACCTacatctcataCT	6.2	0.9	119.2	3.4
  107_2	ACctacatctcataCT	14.3	7.4	142.9	13.7
  108_1	TACCtacatctcataCT	5.6	1.0	127.0	10.7
  108_2	TAcctacatctcataCT	21.4	12.5	117.1	8.5
  109_1	TTacctacatctcaTACT	4.4	0.4	138.9	1.2
  109_2	TTacctacatctcataCT	22.9	3.3	117.1	13.0
  110_1	TTAcctacatctcaTAC	8.7	2.1	133.2	5.1
  110_2	TTacctacatctcatAC	21.0	5.1	111.4	11.1
  111_1	GTtacctacatctCATA	8.0	2.4	143.8	14.8
  111_2	GTtacctacatctcaTA	19.0	2.3	115.4	4.1
  112_1	GTTacctacatctCAT	6.6	1.4	145.5	16.8
  112_2	GTtacctacatctcAT	15.8	4.5	120.3	8.1
  126_1	TCACtttccagatatCA	8.0	1.9	133.8	5.4
  126_3	TCactttccagatatCA	53.4	75.9	112.0	11.4
  128_1	ACATgtccctttataTT	16.3	2.5	114.7	11.1
  128_2	ACatgtccctttataTT	14.8	1.1	136.9	6.2
  129_1	ACAtgtccctttaTAT	11.8	1.9	135.0	14.3
  132_1	CTCAtccctccaagaAA	9.1	1.6	131.7	8.4
  132_2	CTcatccctccaagaAA	11.2	3.9	159.3	17.7

Example 2—Oligonucleotide Activity in Human Neuronal Cell Cultures
• Oligonucleotides targeting human SNHG14 in the region downstream of SNORD109B corresponding to position 25278410 to 25419462 on chromosome 15 (SEQ ID NO: 1) were tested in patient derived human neuronal cell cultures (see protocol in “Materials and methods” section). The oligonucleotides ability to reduce the SNHG14 transcript in the region downstream of SNORD109B (also termed UBE3A suppressor or UBE3A-SUP in the data table), without affecting expression of SNORD115 was analyzed. Furthermore, the ability to induce UBE3A mRNA re-expression was analyzed.
• The oligonucleotides were screened according to the protocol for screening oligonucleotides in human neuronal cell cultures described in the section “Materials and methods” above.
• The results are shown in table 5. The expression of UBE3A mRNA has been measured for all compounds, whereas the knock-down of the UBE3A suppressor and the maintenance of SNORD1115 levels have not been analyzed for all compounds.

• TABLE 5
  Oligonucleotide activity in patient derived human neuronal cell cultures.

  Start			% of Mock		% of Mock		% of Mock
  SEQ ID	CMP		Oligo conc		Oligo conc		Oligo conc
  NO 1	ID NO	Target	0.2 μM	sd	1.0 μM	sd	5.0 μM	sd

  1678	10_1	UBE3A	107	14	88	10	151	8
  1679	12_2	UBE3A	100	9	87	14	158	16
  1687	20_1	UBE3A	87	7	102	22	213	44
  1712	21_1	UBE3A	127	23	166	6	178	13
  1712	21_1	UBE3A-SUP	81	3	82	8	72	12
  1712	21_1	SNORD115	115	6	142	24	169	26
  4167	22_1	UBE3A	87	5	90	8	146	20
  4170	27_1	UBE3A	94	16	106	11	170	10
  4171	29_2	UBE3A	86	13	100	12	194	35
  4172	30_1	UBE3A	96	6	121	12	209	27
  9210	35_1	UBE3A	88	5	112	23	195	27
  10838	37_1	UBE3A	77	7	85	9	169	24
  15565	38_2	UBE3A	93	11	108	6	167	34
  22209	42_1	UBE3A	125	16	143	14	180	17
  22209	42_1	UBE3A-SUP	108	14	98	15	85	18
  22209	42_1	SNORD115	101	14	93	25	127	21
  30449	43_1	UBE3A	99	5	95	13	115	8
  30451	44_1	UBE3A	99	15	80	20	141	17
  30451	44_2	UBE3A	98	31	104	16	119	7
  30697	46_1	UBE3A	91	8	87	5	167	20
  36066	49_1	UBE3A	95	6	111	10	155	29
  36066	49_1	UBE3A-SUP	76	7	84	24	110	31
  36066	49_1	SNORD115	99	14	111	20	94	6
  36068	50_1	UBE3A	109	15	105	11	92	14
  36068	50_1	UBE3A-SUP	122	24	93	28	73	7
  36068	50_1	SNORD115	120	15	113	12	99	6
  37206	51_1	UBE3A	114	16	101	7	101	3
  37206	51_1	UBE3A-SUP	128	21	67	9	84	13
  37206	51_1	SNORD115	140	26	110	9	100	11
  46130	52_1	UBE3A	139	3	160	1	236	36
  46130	52_1	UBE3A-SUP	135	16	133	26	160	32
  46130	52_1	SNORD115	104	8	119	14	100	8
  48145	59_1	UBE3A	179	3	122	17	115	NA
  48170	76_1	UBE3A	85	16	100	8	155	12
  48171	80_1	UBE3A	120	7	114	10	172	20
  48171	78_1	UBE3A	136	31	103	20	169	11
  48172	82_2	UBE3A	96	11	121	4	186	32
  48172	84_1	UBE3A	95	14	100	8	158	14
  49343	85_1	UBE3A	97	22	121	10	189	17
  49722	87_1	UBE3A	111	9	126	11	177	22
  52417	92_1	UBE3A	133	7	140	30	140	8
  52417	92_1	UBE3A-SUP	88	14	80	14	82	8
  52417	92_1	SNORD115	102	8	114	20	91	9
  52420	93_1	UBE3A	111	14	120	9	126	16
  52420	93_1	UBE3A-SUP	104	23	82	20	79	8
  52420	93_1	SNORD115	110	11	114	17	95	7
  53953	94_1	UBE3A	117	12	147	15	166	15
  53953	94_1	UBE3A-SUP	92	18	81	5	86	22
  53953	94_1	SNORD115	124	33	122	17	106	14
  60819	95_1	UBE3A	103	11	131	14	175	7
  60819	95_1	UBE3A-SUP	93	13	87	3	74	6
  60819	95_1	SNORD115	162	19	158	20	201	11
  60819	95_2	UBE3A	147	10	129	20	117	2
  60819	95_2	UBE3A-SUP	118	24	87	13	83	8
  60819	95_2	SNORD115	104	17	118	10	129	6
  60823	96_1	UBE3A	115	16	135	19	174	17
  60823	96_1	UBE3A-SUP	104	25	93	32	91	11
  60823	96_2	UBE3A	108	7	114	9	115	13
  60823	96_2	UBE3A-SUP	99	17	92	19	93	10
  60824	97_1	UBE3A	111	12	134	23	169	14
  60824	97_1	UBE3A-SUP	110	27	105	33	92	10
  60824	97_2	UBE3A	124	13	126	12	124	11
  60824	97_2	UBE3A-SUP	113	17	107	33	96	20
  60824	98_1	UBE3A	111	16	119	11	138	14
  60824	98_1	UBE3A-SUP	118	34	98	23	82	19
  60824	98_1	SNORD115	109	11	123	18	114	16
  60824	98_2	UBE3A	128	10	109	7	136	12
  60824	98_2	UBE3A-SUP	91	15	77	11	110	16
  60824	98_2	SNORD115	101	3	110	7	124	11
  60825	99_1	UBE3A	125	6	115	5	131	10
  60825	99_1	UBE3A-SUP	139	18	121	34	127	45
  60825	99_1	SNORD115	110	18	112	12	99	19
  60825	99_2	UBE3A	120	21	111	11	135	22
  60825	99_2	UBE3A-SUP	96	21	79	15	75	11
  60825	99_2	SNORD115	104	34	113	22	131	24
  60825	100_1	UBE3A	123	34	139	34	145	21
  60825	100_1	UBE3A-SUP	104	37	127	46	99	17
  60825	100_2	UBE3A	124	46	138	37	145	31
  60825	100_2	UBE3A-SUP	111	36	120	47	92	11
  60825	101_1	UBE3A	112	18	123	15	150	13
  60825	101_1	UBE3A-SUP	96	18	102	14	88	12
  60825	101_2	UBE3A	118	15	138	24	139	32
  60825	101_2	UBE3A-SUP	100	29	110	39	92	10
  60826	102_1	UBE3A	132	17	120	7	125	9
  60826	102_1	UBE3A-SUP	113	16	83	5	88	18
  60826	102_1	SNORD115	121	36	131	23	100	9
  60826	102_2	UBE3A	90	6	116	23	103	7
  60826	102_2	UBE3A-SUP	91	7	90	12	64	18
  60826	102_2	SNORD115	116	15	146	27	183	28
  60827	103_1	UBE3A	106	8	112	10	115	9
  60827	103_1	UBE3A-SUP	99	15	110	28	94	8
  60827	103_2	UBE3A	107	14	120	13	112	14
  60827	103_2	UBE3A-SUP	97	14	118	38	93	20
  60827	104_1	UBE3A	128	14	111	9	111	6
  60827	104_1	UBE3A-SUP	111	12	97	9	87	19
  60827	104_1	SNORD115	114	10	110	12	109	13
  60827	104_2	UBE3A	108	10	111	16	109	10
  60827	104_2	UBE3A-SUP	103	13	103	33	89	9
  60827	105_1	UBE3A	122	13	121	12	121	4
  60827	105_1	UBE3A-SUP	119	7	97	15	93	7
  60827	105_1	SNORD115	114	21	128	12	118	9
  60827	105_2	UBE3A	123	5	110	9	114	8
  60827	105_2	UBE3A-SUP	110	11	89	17	94	21
  60827	105_2	SNORD115	102	15	108	16	107	18
  60827	106_1	UBE3A	114	17	133	23	125	9
  60827	106_1	UBE3A-SUP	112	35	103	15	87	12
  60827	106_2	UBE3A	110	12	130	22	123	14
  60827	106_2	UBE3A-SUP	105	19	107	27	93	10
  60828	107_1	UBE3A	83	11	117	13	112	6
  60828	107_1	UBE3A-SUP	86	11	114	16	67	7
  60828	107_1	SNORD115	108	17	130	21	137	24
  60828	107_2	UBE3A	143	42	117	10	122	11
  60828	107_2	UBE3A-SUP	116	12	92	4	100	8
  60828	107_2	SNORD115	108	4	127	16	108	14
  60828	108_1	UBE3A	120	7	127	31	132	31
  60828	108_1	UBE3A-SUP	153	33	118	34	89	17
  60828	108_1	SNORD115	114	9	114	9	105	15
  60828	108_2	UBE3A	122	18	133	26	128	9
  60828	108_2	UBE3A-SUP	101	19	100	28	89	17
  60828	109_1	UBE3A	108	10	129	14	128	5
  60828	109_1	UBE3A-SUP	106	21	107	24	84	8
  60828	109_2	UBE3A	109	11	110	8	111	13
  60828	109_2	UBE3A-SUP	95	15	86	14	83	9
  60829	110_1	UBE3A	104	6	83	3	101	15
  60829	110_1	UBE3A-SUP	100	13	95	12	79	4
  60829	110_1	SNORD115	126	21	125	6	182	13
  60829	110_2	UBE3A	92	7	87	8	96	7
  60829	110_2	UBE3A-SUP	99	7	108	9	81	5
  60829	110_2	SNORD115	118	15	139	22	198	39
  60830	111_1	UBE3A	110	6	122	13	124	10
  60830	111_1	UBE3A-SUP	104	14	90	28	79	11
  60830	111_2	UBE3A	115	10	120	15	121	10
  60830	111_2	UBE3A-SUP	114	20	89	19	87	9
  60831	112_1	UBE3A	93	8	94	13	106	10
  60831	112_1	UBE3A-SUP	97	1	68	29	82	7
  60831	112_1	SNORD115	116	20	110	13	158	20
  60831	112_2	UBE3A	83	8	78	7	83	6
  60831	112_2	UBE3A-SUP	106	35	80	23	69	9
  60831	112_2	SNORD115	107	6	106	8	159	21
  62198	113_1	UBE3A	110	3	122	6	134	9
  62198	113_1	UBE3A-SUP	113	20	85	19	79	24
  62198	113_1	SNORD115	116	18	123	9	91	9
  62284	115_1	UBE3A	105	14	98	19	141	36
  62422	116_1	UBE3A	130	19	142	29	172	18
  62423	117_1	UBE3A	76	8	93	13	171	17
  62439	118_1	UBE3A	75	7	88	9	150	19
  66378	119_1	UBE3A	96	14	93	5	110	10
  77565	126_1	UBE3A	94	6	113	5	125	14
  77565	126_1	UBE3A-SUP	83	17	95	33	85	5
  77565	126_1	SNORD115	105	11	123	19	152	15
  77565	126_2	UBE3A	95	5	126	9	111	2
  77565	126_2	UBE3A-SUP	77	27	106	21	83	15
  77565	126_2	SNORD115	115	17	157	13	180	15
  92321	128_1	UBE3A	102	7	91	5	111	13
  92321	128_1	UBE3A-SUP	115	3	104	25	91	13
  92321	128_1	SNORD115	135	9	132	12	196	35
  92321	128_2	UBE3A	91	5	96	8	104	8
  92321	128_2	UBE3A-SUP	112	20	92	20	79	7
  92321	128_2	SNORD115	125	7	111	13	169	12
  92322	129_1	UBE3A	101	5	103	2	110	7
  92322	129_1	UBE3A-SUP	99	39	113	12	94	13
  92322	129_1	SNORD115	124	25	114	6	140	13
  92322	129_2	UBE3A	93	2	100	4	113	16
  92322	129_2	UBE3A-SUP	109	4	102	22	85	7
  92322	129_2	SNORD115	103	11	99	9	152	31
  97154	132_1	UBE3A	100	10	128	13	142	13
  97154	132_1	UBE3A-SUP	103	9	115	8	109	6
  97154	132_1	SNORD115	49	7	90	12	143	25
  97154	132_2	UBE3A	111	8	128	17	128	17
  97154	132_2	UBE3A-SUP	95	7	116	9	105	13
  97154	133_2	SNORD115	86	7	106	9	121	9
  97154	133_1	UBE3A	101	3	107	11	124	19
  97154	133_1	UBE3A-SUP	112	9	117	7	146	25
  97154	133_1	SNORD115	60	7	110	15	141	15
  97154	133_2	UBE3A	94	13	116	14	138	12
  97154	133_2	UBE3A-SUP	116	6	128	13	148	38
  97154	132_2	SNORD115	70	5	108	9	160	34
  106137	137_1	UBE3A	83	12	74	11	124	20
  109404	138_1	UBE3A	80	20	92	7	120	21
  110766	139_1	UBE3A	76	5	85	12	121	17
  114826	140_1	UBE3A	87	10	88	11	136	9
  118637	143_1	UBE3A	83	7	104	30	141	28
  118639	144_1	UBE3A	74	17	31	39	106	33
  124160	145_2	UBE3A	89	6	95	10	115	25
  125499	146_1	UBE3A	83	13	76	7	124	16
  125499	146_2	UBE3A	123	30	79	14	102	23
  125538	150_2	UBE3A	82	17	82	7	119	24

• Of the 187 compounds tested approximately 90% showed re-expression of UBE3A when compared to the mock oligonucleotide at the 5 micro Molar concentration. The number of oligonucleotides capable of inducing re-expression of UBE3A is higher in the region between position 1 to 55318 of SEQ ID NO: 1 (non-overlapping region) then in the region complementary to UBE3A coding region (overlapping region. FIG. 2 plots the distribution of the oligonucleotides according to their position on chromosome 15 versus the UBE3A mRNA expression relative to the mock oligonucleotide.
• For the oligonucleotides where SNORD115 has been tested there is no significant down regulation when compared to mock at 1 and 5 microM.
Example 3—Activity of Oligonucleotides Targeting the SNHG14 Transcript in the Region Downstream of SNORD109B and Upstream of the Region Antisense to the UBE3A Pre-mRNA
• Oligonucleotides targeting position 4806-54939 of SEQ ID NO: 1 were tested in patient derived human neuronal cell cultures (see protocol in “Materials and methods” section). The oligonucleotides ability to reduce the SNHG14 transcript in the region downstream of SNORD109B (also termed UBE3A suppressor or UBE3A-SUP in the data table. Furthermore, the ability to induce UBE3A mRNA re-expression was analyzed.
• The oligonucleotides were screened according to the protocol for screening oligonucleotides in human neuronal cell cultures described in the section “Materials and methods”—“Screening oligonucleotides in human neuronal cell cultures—96 well system”
• The results are shown in table 6.

• TABLE 6
  Oligonucleotide activity in patient derived human neuronal cell cultures.

  Start SEQ	CMP ID	Conc	% of Mock		% of Mock
  ID NO 1	NO	μM	UBE3A-SUP	sd	UBE3A	sd

  4806	151_1	0.2	66	2	125	NA
  4806	151_1	1	53	10	NA	NA
  4808	152_1	0.2	49	6	167	NA
  4808	152_1	1	33	4	289	NA
  4809	153_1	0.2	41	1	208	NA
  4809	153_1	1	29	10	NA	NA
  4811	154_1	0.2	48	3	282	NA
  4811	154_1	1	37	5	331	NA
  4812	155_1	0.2	35	5	286	64
  4812	155_1	1	32	3	327	21
  4972	156_1	0.2	60	6	145	6
  4972	156_1	1	46	14	145	NA
  4973	157_1	0.2	75	9	128	6
  4973	157_1	1	59	NA	158	NA
  4979	158_1	0.2	46	9	131	NA
  4979	158_1	1	37	5	219	8
  5058	159_1	0.2	69	6	133	19
  5058	159_1	1	51	14	NA	NA
  5071	160_1	0.2	55	8	98	NA
  5071	160_1	1	39	7	136	34
  5078	161_1	0.2	65	7	205	18
  5078	161_1	1	51	10	306	31
  5094	162_1	0.2	53	5	154	27
  5094	162_1	1	34	8	300	65
  5096	163_1	0.2	44	1	206	49
  5096	163_1	1	36	6	316	NA
  5100	164_1	0.2	34	3	220	NA
  5100	164_1	1	30	3	227	32
  5101	165_1	0.2	38	7	245	NA
  5101	165_1	1	36	4	246	55
  5218	166_1	0.2	45	4	240	NA
  5218	166_1	1	36	6	280	44
  5218	167_1	0.2	46	2	261	NA
  5218	167_1	1	31	4	346	30
  5224	168_1	0.2	39	3	377	40
  5224	168_1	1	33	5	338	65
  5224	169_1	0.2	37	4	313	NA
  5224	169_1	1	31	2	308	3
  5427	170_1	0.2	89	13	105	26
  5427	170_1	1	117	35	124	NA
  5434	171_1	0.2	51	5	164	10
  5434	171_1	1	33	6	213	46
  5785	172_1	0.2	46	5	210	NA
  5785	172_1	1	38	4	342	NA
  5786	173_1	0.2	54	4	292	61
  5786	173_1	1	39	6	552	NA
  6341	174_1	0.2	97	11	126	3
  6341	174_1	1	90	33	NA	NA
  6694	175_1	0.2	44	4	226	NA
  6694	175_1	1	35	4	296	NA
  6695	176_1	0.2	32	7	297	87
  6695	176_1	1	29	4	263	9
  6958	177_1	0.2	58	7	244	76
  6958	177_1	1	47	NA	NA	NA
  7159	179_1	0.2	33	4	282	NA
  7159	179_1	1	29	5	289	7
  7159	178_1	0.2	43	5	248	NA
  7159	178_1	1	32	4	258	NA
  7720	180_1	0.2	75	6	144	36
  7720	180_1	1	54	7	233	26
  7724	181_1	0.2	72	6	177	20
  7724	181_1	1	45	19	224	62
  7725	182_1	0.2	65	5	139	37
  7725	182_1	1	47	4	208	76
  7725	183_1	0.2	103	13	140	2
  7725	183_1	1	74	6	NA	NA
  7727	184_1	0.2	45	2	300	107
  7727	184_1	1	35	2	272	16
  8117	185_1	0.2	87	17	122	13
  8117	185_1	1	63	17	175	NA
  8118	186_1	0.2	40	5	368	105
  8118	186_1	1	33	5	NA	NA
  8119	187_1	0.2	62	5	197	NA
  8119	187_1	1	43	13	517	143
  8120	188_1	0.2	96	10	136	41
  8120	188_1	1	79	22	146	19
  8571	189_1	0.2	53	11	204	NA
  8571	189_1	1	49	24	298	15
  8573	190_1	0.2	54	9	140	9
  8573	190_1	1	50	10	267	4
  8574	191_1	0.2	56	1	117	NA
  8574	191_1	1	57	13	199	NA
  8575	192_1	0.2	56	9	165	10
  8575	192_1	1	54	13	246	NA
  8576	193_1	0.2	56	6	185	7
  8576	193_1	1	52	8	330	35
  8585	194_1	0.2	47	2	302	NA
  8585	194_1	1	39	7	NA	NA
  8819	195_1	0.2	62	10	155	10
  8819	195_1	1	41	3	192	7
  8820	196_1	0.2	55	12	237	69
  8820	196_1	1	40	3	278	26
  8887	197_1	0.2	69	15	301	59
  8887	197_1	1	58	7	383	92
  9150	198_1	0.2	49	6	NA	NA
  9150	198_1	1	43	3	365	38
  9201	199_1	0.2	79	23	88	42
  9201	199_1	1	64	24	140	22
  9202	201_1	0.2	61	10	NA	NA
  9202	201_1	1	45	8	343	27
  9202	200_1	0.2	47	3	287	76
  9202	200_1	1	41	4	281	NA
  9203	202_1	0.2	55	17	166	92
  9203	202_1	1	40	5	297	54
  9209	203_1	0.2	60	1	122	NA
  9209	203_1	1	40	14	204	8
  9210	204_1	0.2	43	2	216	NA
  9210	204_1	1	37	3	409	NA
  9210	205_1	0.2	45	8	187	NA
  9210	205_1	1	37	22	336	18
  9211	206_1	0.2	51	10	384	17
  9211	206_1	1	42	3	381	35
  9211	207_1	0.2	65	8	301	28
  9211	207_1	1	50	5	272	53
  9212	35_2	0.2	42	11	203	16
  9212	35_2	1	44	18	335	NA
  9212	208_1	0.2	64	5	147	58
  9212	208_1	1	50	6	260	73
  9213	209_1	0.2	57	7	NA	NA
  9213	209_1	1	49	4	346	31
  9214	210_1	0.2	49	7	139	NA
  9214	210_1	1	45	7	223	59
  10832	211_1	0.2	70	6	147	10
  10832	211_1	1	56	9	200	38
  10837	212_1	0.2	59	9	146	46
  10837	212_1	1	41	6	226	47
  10838	213_1	0.2	50	8	247	69
  10838	213_1	1	44	12	307	NA
  10877	214_1	0.2	108	21	115	1
  10877	214_1	1	92	37	88	32
  11434	215_1	0.2	97	12	81	23
  11434	215_1	1	80	26	111	11
  11435	216_1	0.2	90	16	87	NA
  11435	216_1	1	82	29	82	21
  11436	217_1	0.2	87	6	83	11
  11436	217_1	1	68	26	123	NA
  11438	218_1	0.2	57	5	133	NA
  11438	218_1	1	44	16	188	NA
  11439	219_1	0.2	84	1	93	NA
  11439	219_1	1	66	22	113	29
  11464	220_1	0.2	67	9	209	51
  11464	220_1	1	41	6	256	33
  11507	221_1	0.2	59	6	237	NA
  11507	221_1	1	40	63	320	NA
  11508	222_1	0.2	53	7	195	NA
  11508	222_1	1	48	12	302	NA
  11511	223_1	0.2	41	3	210	6
  11511	223_1	1	37	9	273	NA
  11513	224_1	0.2	22	8	288	91
  11513	224_1	1	26	5	360	46
  11514	225_1	0.2	98	17	98	31
  11514	225_1	1	68	16	129	11
  11736	226_1	0.2	69	8	197	80
  11736	226_1	1	55	7	329	66
  12361	227_1	0.2	48	8	183	56
  12361	227_1	1	37	4	193	46
  12794	228_1	0.2	38	9	201	71
  12794	228_1	1	32	2	362	48
  12795	229_1	0.2	50	12	161	30
  12795	229_1	1	34	7	301	35
  12796	230_1	0.2	44	12	237	86
  12796	230_1	1	32	3	379	106
  12894	232_1	0.2	91	17	79	27
  12894	232_1	1	66	10	99	24
  12894	231_1	0.2	80	5	89	NA
  12894	231_1	1	57	14	164	31
  12895	234_1	0.2	88	11	75	32
  12895	234_1	1	68	19	91	24
  12895	233_1	0.2	57	5	199	37
  12895	233_1	1	38	7	249	57
  12896	235_1	0.2	72	3	176	9
  12896	235_1	1	45	3	251	42
  13223	236_1	0.2	40	3	267	66
  13223	236_1	1	31	3	270	23
  13224	238_1	0.2	33	3	265	NA
  13224	238_1	1	28	4	265	6
  13224	237_1	0.2	38	2	212	NA
  13224	237_1	1	31	1	254	31
  13225	239_1	0.2	42	5	317	113
  13225	239_1	1	29	7	215	26
  13226	240_1	0.2	38	7	223	NA
  13226	240_1	1	32	5	232	16
  15115	241_1	0.2	61	8	377	15
  15115	241_1	1	41	3	377	43
  15258	242_1	0.2	66	14	133	35
  15258	242_1	1	55	10	170	17
  15568	243_1	0.2	62	13	192	58
  15568	243_1	1	41	11	309	5
  15570	244_1	0.2	53	17	252	59
  15570	244_1	1	44	5	332	52
  15572	245_1	0.2	57	21	321	122
  15572	245_1	1	49	7	407	77
  15573	246_1	0.2	47	16	348	129
  15573	246_1	1	40	7	410	69
  15574	247_1	0.2	48	14	326	116
  15574	247_1	1	44	8	411	36
  15722	248_1	0.2	51	3	258	17
  15722	248_1	1	36	3	230	NA
  16597	249_1	0.2	66	19	111	39
  16597	249_1	1	54	14	174	44
  16603	250_1	0.2	67	26	89	31
  16603	250_1	1	56	6	172	32
  16730	251_1	0.2	36	5	354	41
  16730	251_1	1	31	2	326	75
  16849	252_1	0.2	74	17	188	81
  16849	252_1	1	48	17	282	1
  17089	253_1	0.2	70	17	98	37
  17089	253_1	1	62	19	153	13
  17401	254_1	0.2	42	6	209	83
  17401	254_1	1	29	3	327	49
  24290	255_1	0.2	106	13	105	36
  24290	255_1	1	109	21	136	NA
  24296	256_1	0.2	92	20	117	30
  24296	256_1	1	93	15	138	21
  24811	257_1	0.2	85	12	126	4
  24811	257_1	1	74	12	137	17
  25032	258_1	0.2	50	11	329	131
  25032	258_1	1	39	5	411	53
  25033	259_1	0.2	40	10	343	50
  25033	259_1	1	31	3	483	84
  25250	260_1	0.2	33	10	279	42
  25250	260_1	1	33	4	338	65
  25251	261_1	0.2	40	8	209	97
  25251	261_1	1	34	3	370	57
  25718	262_1	0.2	56	20	113	48
  25718	262_1	1	45	8	198	65
  25720	263_1	0.2	84	7	121	39
  25720	263_1	1	72	11	88	10
  25721	264_1	0.2	83	15	87	40
  25721	264_1	1	84	22	NA	NA
  26331	265_1	0.2	93	5	88	38
  26331	265_1	1	81	8	NA	NA
  27165	266_1	0.2	63	3	117	39
  27165	266_1	1	46	9	174	15
  27248	267_1	0.2	81	10	124	17
  27248	267_1	1	59	10	190	112
  29330	268_1	0.2	109	4	124	48
  29330	268_1	1	98	28	114	35
  29635	269_1	0.2	45	1	218	50
  29635	269_1	1	33	9	267	NA
  29635	270_1	0.2	55	5	225	41
  29635	270_1	1	45	8	NA	NA
  29636	271_1	0.2	48	2	285	56
  29636	271_1	1	40	7	359	99
  29636	272_1	0.2	48	3	166	5
  29636	272_1	1	35	8	293	40
  29637	273_1	0.2	56	5	255	47
  29637	273_1	1	46	4	300	105
  29637	274_1	0.2	67	7	134	35
  29637	274_1	1	54	7	234	19
  29661	275_1	0.2	51	3	167	15
  29661	275_1	1	42	11	251	NA
  29661	276_1	0.2	54	5	127	17
  29661	276_1	1	39	8	229	NA
  29684	277_1	0.2	40	3	168	73
  29684	277_1	1	31	13	NA	NA
  29684	278_1	0.2	46	7	179	2
  29684	278_1	1	36	8	NA	NA
  30455	279_1	0.2	102	20	96	34
  30455	279_1	1	86	22	118	23
  30456	280_1	0.2	94	23	91	28
  30456	280_1	1	83	18	134	36
  30457	281_1	0.2	89	23	97	37
  30457	281_1	1	94	23	106	39
  30458	282_1	0.2	99	14	77	27
  30458	282_1	1	103	17	96	20
  30462	283_1	0.2	66	26	98	36
  30462	283_1	1	56	14	129	13
  30465	284_1	0.2	73	11	114	47
  30465	284_1	1	57	10	197	63
  30601	285_1	0.2	41	31	311	29
  30601	285_1	1	30	16	373	40
  30605	286_1	0.2	40	2	221	86
  30605	286_1	1	33	6	375	NA
  30609	287_1	0.2	43	3	267	65
  30609	287_1	1	37	5	332	27
  30610	288_1	0.2	46	6	253	79
  30610	288_1	1	38	3	338	NA
  30667	289_1	0.2	38	15	325	144
  30667	289_1	1	36	3	461	68
  30668	290_1	0.2	74	19	124	54
  30668	290_1	1	58	14	183	20
  30669	291_1	0.2	86	18	98	40
  30669	291_1	1	78	12	133	26
  30670	292_1	0.2	93	10	86	31
  30670	292_1	1	94	16	127	22
  30679	293_1	0.2	85	19	83	21
  30679	293_1	1	87	21	113	23
  30681	294_1	0.2	92	17	78	20
  30681	294_1	1	100	19	86	22
  30682	295_1	0.2	93	22	101	40
  30682	295_1	1	94	33	101	8
  30699	296_1	0.2	80	24	134	6
  30699	296_1	1	47	21	232	36
  30700	297_1	0.2	53	5	146	26
  30700	297_1	1	32	8	NA	NA
  30700	298_1	0.2	47	4	221	NA
  30700	298_1	1	38	0	294	NA
  30701	299_1	0.2	49	4	140	NA
  30701	299_1	1	23	NA	NA	NA
  30701	300_1	0.2	50	9	163	19
  30701	300_1	1	39	11	346	11
  30702	301_1	0.2	66	9	116	36
  30702	301_1	1	44	14	230	51
  30711	302_1	0.2	41	14	288	120
  30711	302_1	1	40	5	422	132
  30714	303_1	0.2	45	9	355	94
  30714	303_1	1	31	5	355	8
  30715	305_1	0.2	39	4	292	56
  30715	305_1	1	34	12	253	5
  30715	304_1	0.2	50	13	263	87
  30715	304_1	1	43	7	285	12
  31630	306_1	0.2	92	32	134	48
  31630	306_1	1	85	25	177	26
  31632	307_1	0.2	94	24	92	32
  31632	307_1	1	86	17	109	33
  31633	308_1	0.2	92	18	78	13
  31633	308_1	1	102	23	98	7
  32755	310_1	0.2	47	12	220	40
  32755	310_1	1	40	16	285	NA
  32755	309_1	0.2	62	6	167	NA
  32755	309_1	1	40	10	225	NA
  32756	311_1	0.2	55	9	128	9
  32756	311_1	1	56	NA	224	NA
  33366	312_1	0.2	64	23	121	4
  33366	312_1	1	56	10	137	1
  33367	313_1	0.2	81	7	91	NA
  33367	313_1	1	79	22	115	12
  33368	314_1	0.2	70	4	103	NA
  33368	314_1	1	57	15	157	NA
  33369	315_1	0.2	73	12	87	20
  33369	315_1	1	67	19	155	NA
  33375	316_1	0.2	79	18	100	18
  33375	316_1	1	51	14	159	39
  33377	317_1	0.2	46	21	248	72
  33377	317_1	1	41	9	313	NA
  33378	318_1	0.2	38	17	273	63
  33378	318_1	1	36	7	321	1
  36606	319_1	0.2	79	10	154	21
  36606	319_1	1	48	9	233	65
  36607	320_1	0.2	60	9	157	18
  36607	320_1	1	49	9	206	25
  38092	321_1	0.2	51	10	221	59
  38092	321_1	1	41	5	328	39
  38297	322_1	0.2	43	9	298	31
  38297	322_1	1	34	6	365	91
  39173	323_1	0.2	98	8	119	27
  39173	323_1	1	82	20	177	21
  39174	324_1	0.2	89	8	139	24
  39174	324_1	1	84	23	192	15
  39175	325_1	0.2	93	18	167	13
  39175	325_1	1	68	17	203	33
  39176	326_1	0.2	79	12	185	83
  39176	326_1	1	55	17	374	107
  39228	327_1	0.2	75	12	151	29
  39228	327_1	1	57	8	207	32
  39230	328_1	0.2	65	11	176	19
  39230	328_1	1	52	19	357	NA
  39231	329_1	0.2	63	19	150	35
  39231	329_1	1	46	6	257	43
  39563	330_1	0.2	69	10	116	34
  39563	330_1	1	56	11	196	NA
  39808	331_1	0.2	40	8	201	17
  39808	331_1	1	25	5	300	NA
  39808	332_1	0.2	40	14	282	109
  39808	332_1	1	33	7	404	81
  39931	333_1	0.2	80	11	107	53
  39931	333_1	1	70	16	112	26
  41114	334_1	0.2	64	4	113	NA
  41114	334_1	1	28	NA	179	NA
  41444	335_1	0.2	57	17	165	39
  41444	335_1	1	46	4	290	40
  41445	336_1	0.2	51	2	134	NA
  41445	336_1	1	42	15	238	NA
  41446	337_1	0.2	63	1	108	NA
  41446	337_1	1	56	14	151	22
  41725	338_1	0.2	91	16	130	50
  41725	338_1	1	75	23	154	27
  41726	339_1	0.2	66	20	142	23
  41726	339_1	1	55	14	193	NA
  41728	340_1	0.2	60	16	137	23
  41728	340_1	1	51	13	233	NA
  42167	341_1	0.2	70	9	138	7
  42167	341_1	1	51	11	182	20
  42168	343_1	0.2	67	9	210	92
  42168	343_1	1	52	6	193	NA
  42168	342_1	0.2	51	6	183	NA
  42168	342_1	1	46	10	275	14
  42169	344_1	0.2	55	1	231	32
  42169	344_1	1	35	3	NA	NA
  42169	345_1	0.2	55	7	164	41
  42169	345_1	1	45	5	284	27
  42287	346_1	0.2	66	7	144	32
  42287	346_1	1	53	5	279	34
  42289	347_1	0.2	75	20	125	10
  42289	347_1	1	68	7	241	69
  43452	348_1	0.2	62	12	231	92
  43452	348_1	1	48	23	257	72
  43453	349_1	0.2	52	11	142	41
  43453	349_1	1	44	23	257	34
  43562	350_1	0.2	50	13	148	35
  43562	350_1	1	36	10	NA	NA
  43565	351_1	0.2	71	10	116	43
  43565	351_1	1	60	11	154	37
  43566	352_1	0.2	65	19	139	14
  43566	352_1	1	44	8	255	23
  43634	353_1	0.2	63	25	172	75
  43634	353_1	1	51	22	214	NA
  44180	355_1	0.2	60	6	165	8
  44180	355_1	1	57	25	145	NA
  44180	354_1	0.2	76	17	149	55
  44180	354_1	1	48	10	240	29
  44181	356_1	0.2	60	5	170	27
  44181	356_1	1	43	15	154	55
  44183	357_1	0.2	50	15	214	33
  44183	357_1	1	37	17	196	19
  44184	358_1	0.2	57	5	155	31
  44184	358_1	1	47	10	257	94
  44439	359_1	0.2	46	4	220	53
  44439	359_1	1	45	2	347	52
  44440	360_1	0.2	48	9	261	37
  44440	360_1	1	44	6	NA	NA
  44440	361_1	0.2	43	5	218	46
  44440	361_1	1	29	3	291	19
  44441	362_1	0.2	50	5	192	60
  44441	362_1	1	45	7	290	58
  44441	363_1	0.2	45	10	185	51
  44441	363_1	1	43	10	247	NA
  44442	364_1	0.2	54	8	124	24
  44442	364_1	1	39	5	271	54
  44442	365_1	0.2	59	6	166	9
  44442	365_1	1	44	8	313	47
  44443	367_1	0.2	55	10	161	29
  44443	367_1	1	40	7	314	67
  44443	366_1	0.2	51	5	202	44
  44443	366_1	1	41	10	300	31
  44477	368_1	0.2	73	6	155	58
  44477	368_1	1	52	3	362	141
  44478	369_1	0.2	82	18	130	35
  44478	369_1	1	58	11	228	66
  44776	370_1	0.2	60	7	128	20
  44776	370_1	1	46	5	274	NA
  45216	371_1	0.2	50	10	149	33
  45216	371_1	1	41	8	260	59
  45217	372_1	0.2	59	7	132	45
  45217	372_1	1	39	4	270	12
  45217	373_1	0.2	47	3	167	52
  45217	373_1	1	38	4	330	62
  45218	374_1	0.2	51	9	189	27
  45218	374_1	1	42	9	359	93
  45246	375_1	0.2	61	8	175	29
  45246	375_1	1	50	7	257	NA
  45247	376_1	0.2	84	4	116	40
  45247	376_1	1	74	10	144	NA
  45248	378_1	0.2	61	10	226	2
  45248	378_1	1	50	5	367	141
  45248	377_1	0.2	74	11	138	29
  45248	377_1	1	62	4	251	NA
  45249	379_1	0.2	48	5	232	NA
  45249	379_1	1	50	NA	312	NA
  45249	380_1	0.2	54	4	203	16
  45249	380_1	1	53	1	353	12
  45250	381_1	0.2	48	6	230	25
  45250	381_1	1	40	7	387	79
  45250	382_1	0.2	60	7	153	30
  45250	382_1	1	46	3	288	43
  45258	383_1	0.2	46	4	211	NA
  45258	383_1	1	34	6	307	29
  45266	385_1	0.2	80	34	85	8
  45266	385_1	1	55	13	128	25
  45266	384_1	0.2	92	4	128	50
  45266	384_1	1	79	12	108	23
  45267	386_1	0.2	93	23	105	13
  45267	386_1	1	80	23	139	14
  45268	387_1	0.2	90	17	111	1
  45268	387_1	1	109	9	122	44
  45270	388_1	0.2	97	7	146	47
  45270	388_1	1	88	9	113	22
  45271	390_1	0.2	79	12	141	14
  45271	390_1	1	58	14	197	38
  45271	389_1	0.2	70	3	97	28
  45271	389_1	1	53	6	150	26
  45272	391_1	0.2	61	4	128	24
  45272	391_1	1	55	14	208	39
  45560	392_1	0.2	86	22	97	26
  45560	392_1	1	71	19	125	18
  45627	393_1	0.2	48	14	150	64
  45627	393_1	1	39	1	209	35
  45628	394_1	0.2	51	4	174	34
  45628	394_1	1	44	8	309	30
  45629	395_1	0.2	60	5	151	24
  45629	395_1	1	48	7	297	43
  45629	396_1	0.2	86	24	139	55
  45629	396_1	1	64	13	203	38
  45635	397_1	0.2	50	10	289	61
  45635	397_1	1	46	2	401	56
  45709	398_1	0.2	47	6	207	61
  45709	398_1	1	49	6	233	NA
  45709	399_1	0.2	56	6	206	13
  45709	399_1	1	45	4	287	93
  46215	400_1	0.2	78	14	122	13
  46215	400_1	1	60	9	114	19
  46256	401_1	0.2	62	7	164	56
  46256	401_1	1	45	5	213	20
  46257	404_1	0.2	44	4	207	44
  46257	404_1	1	41	3	288	45
  46257	402_1	0.2	48	5	197	57
  46257	402_1	1	41	1	300	11
  46257	403_1	0.2	51	4	265	50
  46257	403_1	1	44	5	382	NA
  46259	405_1	0.2	46	4	NA	NA
  46259	405_1	1	39	10	359	10
  46260	406_1	0.2	52	9	153	63
  46260	406_1	1	48	7	262	71
  46263	407_1	0.2	52	9	148	9
  46263	407_1	1	41	5	262	45
  46264	408_1	0.2	51	17	269	72
  46264	408_1	1	42	8	280	55
  46392	409_1	0.2	38	10	359	91
  46392	409_1	1	38	8	NA	NA
  46393	410_1	0.2	39	12	295	30
  46393	410_1	1	32	12	NA	NA
  46420	411_1	0.2	75	10	69	3
  46420	411_1	1	86	3	101	21
  46505	412_1	0.2	65	11	97	7
  46505	412_1	1	53	5	226	59
  46505	413_1	0.2	74	16	124	19
  46505	413_1	1	69	13	117	11
  46506	414_1	0.2	75	7	149	17
  46506	414_1	1	71	10	169	118
  46507	415_1	0.2	86	31	119	36
  46507	415_1	1	66	17	129	28
  46508	416_1	0.2	86	22	87	22
  46508	416_1	1	67	10	142	16
  47364	417_1	0.2	49	2	166	22
  47364	417_1	1	47	13	295	NA
  47365	418_1	0.2	54	3	131	29
  47365	418_1	1	41	3	230	42
  48110	419_1	0.2	77	9	101	45
  48110	419_1	1	58	8	178	68
  48111	420_1	0.2	63	7	121	32
  48111	420_1	1	51	2	238	59
  48186	421_1	0.2	69	5	176	52
  48186	421_1	1	44	12	307	62
  48221	422_1	0.2	58	15	149	63
  48221	422_1	1	39	6	235	50
  48222	423_1	0.2	60	12	143	9
  48222	423_1	1	43	10	209	57
  49345	85_2	0.2	43	14	242	38
  49345	85_2	1	37	5	275	NA
  50282	424_1	0.2	75	20	138	19
  50282	424_1	1	56	9	226	62
  51241	426_1	0.2	61	6	144	NA
  51241	426_1	1	46	9	264	44
  51241	425_1	0.2	46	8	164	22
  51241	425_1	1	44	4	244	35
  51242	428_1	0.2	57	6	138	30
  51242	428_1	1	48	7	290	39
  51242	427_1	0.2	40	15	341	NA
  51242	427_1	1	30	8	286	63
  51244	429_1	0.2	46	5	184	25
  51244	429_1	1	44	6	283	4
  51245	430_1	0.2	47	7	203	9
  51245	430_1	1	37	5	271	29
  51358	431_1	0.2	51	7	265	10
  51358	431_1	1	40	4	363	70
  51358	432_1	0.2	60	4	202	51
  51358	432_1	1	37	7	275	NA
  51359	433_1	0.2	40	3	238	20
  51359	433_1	1	32	3	NA	NA
  51359	434_1	0.2	39	6	424	83
  51359	434_1	1	35	6	360	NA
  51438	435_1	0.2	78	15	144	62
  51438	435_1	1	60	14	201	27
  51438	436_1	0.2	71	4	125	32
  51438	436_1	1	54	6	205	71
  51953	437_1	0.2	46	6	217	35
  51953	437_1	1	37	4	277	52
  52150	438_1	0.2	67	6	131	39
  52150	438_1	1	53	13	177	NA
  52549	439_1	0.2	56	5	162	31
  52549	439_1	1	50	10	215	39
  52550	440_1	0.2	69	13	137	40
  52550	440_1	1	50	5	156	53
  52551	441_1	0.2	66	3	132	8
  52551	441_1	1	49	5	169	27
  52579	442_1	0.2	38	7	280	60
  52579	442_1	1	37	5	257	51
  53012	443_1	0.2	79	10	197	61
  53012	443_1	1	65	7	212	36
  53013	445_1	0.2	64	6	211	13
  53013	445_1	1	56	4	264	42
  53013	444_1	0.2	68	11	137	33
  53013	444_1	1	58	9	198	35
  53014	446_1	0.2	59	6	125	NA
  53014	446_1	1	47	3	216	22
  53014	447_1	0.2	53	2	188	94
  53014	447_1	1	51	10	192	47
  54198	448_1	0.2	54	15	161	66
  54198	448_1	1	48	11	243	NA
  54199	449_1	0.2	63	12	166	20
  54199	449_1	1	45	8	185	41
  54232	450_1	0.2	84	17	112	67
  54232	450_1	1	83	8	157	15
  54233	451_1	0.2	67	14	118	44
  54233	451_1	1	51	8	192	34
  54235	452_1	0.2	50	3	162	NA
  54235	452_1	1	42	7	190	NA
  54236	453_1	0.2	47	21	234	17
  54236	453_1	1	42	5	295	NA
  54238	454_1	0.2	76	14	85	NA
  54238	454_1	1	48	12	162	NA
  54239	455_1	0.2	62	6	132	69
  54239	455_1	1	46	7	149	57
  54609	456_1	0.2	66	10	130	57
  54609	456_1	1	56	11	141	60
  54924	457_1	0.2	78	3	137	29
  54924	457_1	1	61	4	178	25

Example 4—Activity of Oligonucleotides Targeting the SNHG14 Transcript in the Region Antisense to the UBE3A Pre-mRNA
• Oligonucleotides targeting position 55337-136214 of SEQ ID NO: 1 were tested in patient derived human neuronal cell cultures (see protocol in “Materials and methods” section). The oligonucleotides ability to reduce the SNHG14 transcript in the region downstream of SNORD109B (also termed UBE3A suppressor or UBE3A-SUP in the data table). Furthermore, the ability to induce UBE3A mRNA re-expression was analyzed.
• The oligonucleotides were screened according to the protocol for screening oligonucleotides in human neuronal cell cultures described in the section “Materials and methods”—“Screening oligonucleotides in human neuronal cell cultures—96 well system”.
• The results are shown in table 7.

• TABLE 7
  Oligonucleotide activity in patient derived human neuronal cell cultures.

  Start SEQ	CMP ID	Conc	% of Mock		% of Mock
  ID NO 1	NO	μM	UBE3A-SUP	sd	UBE3A	sd

  55337	458_1	0.2	64	0	177	6
  55337	458_1	1	50	10	233	9
  55338	459_1	0.2	48	1	186	6
  55338	459_1	1	44	9	213	NA
  59565	460_1	0.2	66	4	110	24
  59565	460_1	1	66	9	131	23
  59574	461_1	0.2	56	5	162	19
  59574	461_1	1	45	13	149	6
  59575	462_1	0.2	56	7	114	84
  59575	462_1	1	39	11	101	13
  59576	463_1	0.2	82	19	52	NA
  59576	463_1	1	65	15	95	18
  60012	464_1	0.2	47	5	129	71
  60012	464_1	1	41	3	160	64
  60298	465_1	0.2	49	7	206	95
  60298	465_1	1	37	9	222	44
  60448	466_1	0.2	47	7	130	NA
  60448	466_1	1	33	8	167	31
  60821	467_1	0.2	87	1	73	NA
  60821	467_1	1	62	18	101	3
  61925	468_1	0.2	108	19	105	19
  61925	468_1	1	95	17	101	19
  62287	469_1	0.2	62	8	180	57
  62287	469_1	1	48	5	196	38
  62422	470_1	0.2	71	2	130	20
  62422	470_1	1	57	9	116	18
  62443	471_1	0.2	51	2	NA	NA
  62443	471_1	1	43	2	160	34
  64113	472_1	0.2	95	4	83	22
  64113	472_1	1	76	14	74	36
  64461	473_1	0.2	79	23	141	22
  64461	473_1	1	59	12	279	53
  64462	474_1	0.2	80	12	138	3
  64462	474_1	1	84	15	202	3
  65272	475_1	0.2	77	3	104	2
  65272	475_1	1	75	23	113	10
  66840	476_1	0.2	67	5	86	5
  66840	476_1	1	72	10	100	12
  67426	477_1	0.2	62	15	101	8
  67426	477_1	1	65	13	170	52
  68194	478_1	0.2	53	10	109	6
  68194	478_1	1	59	4	178	7
  68328	479_1	0.2	74	6	94	2
  68328	479_1	1	79	16	111	38
  68805	480_1	0.2	58	15	157	63
  68805	480_1	1	49	2	190	26
  68921	481_1	0.2	58	7	210	58
  68921	481_1	1	55	10	281	NA
  70133	482_1	0.2	50	9	149	6
  70133	482_1	1	54	8	247	41
  72377	483_1	0.2	44	2	143	NA
  72377	483_1	1	52	6	195	37
  72378	484_1	0.2	47	12	111	8
  72378	484_1	1	56	3	201	NA
  72826	485_1	0.2	54	12	116	0
  72826	485_1	1	64	13	172	1
  72861	486_1	0.2	52	9	93	6
  72861	486_1	1	54	6	167	16
  72887	487_1	0.2	55	3	128	5
  72887	487_1	1	59	4	193	24
  73474	488_1	0.2	55	10	132	20
  73474	488_1	1	55	5	202	56
  73992	489_1	0.2	60	7	146	17
  73992	489_1	1	67	7	197	31
  74791	490_1	0.2	42	5	167	65
  74791	490_1	1	46	6	277	19
  74851	491_1	0.2	69	14	78	1
  74851	491_1	1	73	6	114	11
  74853	492_1	0.2	64	6	84	1
  74853	492_1	1	68	5	136	25
  75840	493_1	0.2	40	10	90	6
  75840	493_1	1	61	8	155	32
  75841	494_1	0.2	65	10	131	30
  75841	494_1	1	57	4	119	16
  76238	495_1	0.2	70	9	109	41
  76238	495_1	1	50	8	156	22
  76254	496_1	0.2	67	13	134	34
  76254	496_1	1	55	7	201	NA
  76811	497_1	0.2	83	7	134	41
  76811	497_1	1	77	8	148	32
  77114	498_1	0.2	59	2	128	13
  77114	498_1	1	64	10	206	NA
  80468	499_1	0.2	55	2	105	34
  80468	499_1	1	61	6	151	42
  81047	500_1	0.2	103	17	80	6
  81047	500_1	1	143	25	122	7
  82233	501_1	0.2	57	NA	104	NA
  82233	501_1	1	61	3	199	39
  84166	502_1	0.2	49	6	89	0
  84166	502_1	1	57	5	115	NA
  85392	503_1	0.2	61	6	90	14
  85392	503_1	1	62	8	118	15
  86974	504_1	0.2	73	7	82	4
  86974	504_1	1	79	3	104	19
  87728	505_1	0.2	79	14	76	2
  87728	505_1	1	80	19	97	35
  87810	506_1	0.2	69	9	101	20
  87810	506_1	1	73	6	155	2
  88417	507_1	0.2	45	NA	116	3
  88417	507_1	1	61	14	168	6
  88991	508_1	0.2	51	6	113	20
  88991	508_1	1	59	2	154	31
  90228	509_1	0.2	65	6	76	10
  90228	509_1	1	62	7	118	4
  90474	510_1	0.2	71	7	83	14
  90474	510_1	1	81	3	125	NA
  91625	511_1	0.2	57	17	105	3
  91625	511_1	1	65	11	150	NA
  91885	512_1	0.2	57	5	105	1
  91885	512_1	1	66	7	155	30
  92976	513_1	0.2	67	6	136	44
  92976	513_1	1	68	11	138	38
  94304	514_1	0.2	81	11	110	7
  94304	514_1	1	87	6	153	28
  94528	515_1	0.2	48	5	128	6
  94528	515_1	1	55	3	191	25
  95653	516_1	0.2	57	3	108	7
  95653	516_1	1	62	3	131	16
  96751	517_1	0.2	63	9	90	19
  96751	517_1	1	62	4	106	NA
  97636	518_1	0.2	49	5	107	14
  97636	518_1	1	44	9	137	NA
  98480	519_1	0.2	55	1	106	NA
  98480	519_1	1	54	5	112	23
  98481	520_1	0.2	55	2	116	6
  98481	520_1	1	62	4	129	6
  99646	521_1	0.2	74	10	105	1
  99646	521_1	1	87	13	119	27
  100334	522_1	0.2	49	7	157	28
  100334	522_1	1	57	2	120	37
  101110	523_1	0.2	51	10	96	10
  101110	523_1	1	72	14	114	25
  101898	524_1	0.2	85	11	79	3
  101898	524_1	1	93	21	92	46
  102558	525_1	0.2	82	9	104	8
  102558	525_1	1	86	18	104	30
  103589	526_1	0.2	85	17	114	14
  103589	526_1	1	94	39	126	6
  104309	527_1	0.2	63	11	148	2
  104309	527_1	1	70	26	155	NA
  105686	528_1	0.2	66	11	91	24
  105686	528_1	1	66	14	140	36
  107972	529_1	0.2	84	15	109	15
  107972	529_1	1	94	14	127	24
  108257	530_1	0.2	63	7	114	19
  108257	530_1	1	67	12	141	40
  109407	531_1	0.2	84	24	87	16
  109407	531_1	1	82	11	127	26
  110210	532_1	0.2	72	12	91	14
  110210	532_1	1	80	14	122	40
  110768	533_1	0.2	67	8	126	16
  110768	533_1	1	87	21	176	45
  111811	534_1	0.2	77	2	98	17
  111811	534_1	1	74	6	143	14
  111812	535_1	0.2	64	4	97	0
  111812	535_1	1	77	3	136	37
  112149	536_1	0.2	73	2	63	2
  112149	536_1	1	77	18	127	36
  112150	537_1	0.2	76	6	78	8
  112150	537_1	1	90	29	91	11
  112945	538_1	0.2	69	4	121	2
  112945	538_1	1	83	14	102	39
  113533	539_1	0.2	95	17	85	2
  113533	539_1	1	91	27	87	17
  114274	540_1	0.2	89	11	103	17
  114274	540_1	1	87	26	132	20
  114495	541_1	0.2	76	5	88	1
  114495	541_1	1	83	15	120	6
  114831	542_1	0.2	59	3	76	4
  114831	542_1	1	74	3	104	4
  115355	543_1	0.2	66	8	91	9
  115355	543_1	1	74	16	110	NA
  116105	544_1	0.2	55	12	77	NA
  116105	544_1	1	74	6	110	8
  116106	545_1	0.2	58	18	96	9
  116106	545_1	1	66	8	130	10
  117096	546_1	0.2	69	9	118	20
  117096	546_1	1	65	4	146	NA
  117189	547_1	0.2	69	6	98	9
  117189	547_1	1	74	11	146	25
  117476	548_1	0.2	59	4	87	5
  117476	548_1	1	65	3	104	10
  118293	549_1	0.2	55	8	92	3
  118293	549_1	1	66	10	105	24
  118294	550_1	0.2	55	18	90	4
  118294	550_1	1	72	21	119	5
  118756	551_1	0.2	60	13	86	18
  118756	551_1	1	88	24	120	26
  119621	552_1	0.2	77	21	117	4
  119621	552_1	1	102	19	146	NA
  120655	553_1	0.2	55	9	124	19
  120655	553_1	1	57	7	185	14
  123733	554_1	0.2	74	6	87	14
  123733	554_1	1	77	4	127	4
  124163	555_1	0.2	89	12	117	46
  124163	555_1	1	67	20	152	13
  125512	556_1	0.2	70	5	114	26
  125512	556_1	1	69	11	119	47
  126882	557_1	0.2	78	15	106	8
  126882	557_1	1	84	10	113	33
  127105	558_1	0.2	71	7	91	13
  127105	558_1	1	68	5	108	28
  127809	559_1	0.2	59	4	74	NA
  127809	559_1	1	58	7	101	26
  129020	560_1	0.2	82	11	103	39
  129020	560_1	1	77	9	103	27
  129205	561_1	0.2	75	24	78	16
  129205	561_1	1	89	11	102	23
  129928	562_1	0.2	57	0	98	21
  129928	562_1	1	63	9	107	18
  130020	563_1	0.2	65	5	85	9
  130020	563_1	1	65	3	145	12
  130884	564_1	0.2	81	24	117	31
  130884	564_1	1	83	4	139	17
  130886	565_1	0.2	80	8	103	13
  130886	565_1	1	69	7	122	11
  131404	566_1	0.2	79	4	85	3
  131404	566_1	1	80	7	116	24
  132514	567_1	0.2	71	8	98	28
  132514	567_1	1	69	9	97	29
  133367	568_1	0.2	78	9	88	16
  133367	568_1	1	91	17	88	32
  136198	569_1	0.2	88	5	87	2
  136198	569_1	1	81	6	109	35

Example 5—Activity of Oligonucleotides Targeting the SNHG14 Transcript in the Region Downstream of SNORD109B and Upstream of the Region Antisense to the UBE3A Pre-mRNA
• Oligonucleotides targeting position 5224-51257 of SEQ ID NO: 1 were tested in patient derived human neuronal cell cultures (see protocol in “Materials and methods” section). The oligonucleotides ability to reduce the SNHG14 transcript in the region downstream of SNORD109B (also termed UBE3A suppressor or UBE3A-SUP in the data table. Furthermore, the ability to induce UBE3A mRNA re-expression was analyzed.
• The oligonucleotides were screened according to the protocol for screening oligonucleotides in human neuronal cell cultures described in the section “Materials and methods” “Screening oligonucleotides in human neuronal cell cultures—96 well system” with the following modifications:
UBE3a-Sense Primer
• Using commercially available primers and probe from ThermoFisher: Hs00166580_m1 amplifying a 94 bp sequence in position 838 of refseq ID NM_000462.3.
• Each plate include PBS controls (instead on a non-targeting ologinucleotide) and a positive control oligonucleotide CMP ID NO: 271_1, resulting in up-regulation of UBE3A mRNA. The additional control oligonucleotides were not included.
• Data are presented as average % expression relative to PBS controls across all plates and normalized to the positive control oligonucleotide to manage plate to plate variation in efficacy levels. The results are shown in table 8.

• TABLE 8
  Oligonucleotide activity in patient
  derived human neuronal cell cultures.

  Start SEQ	CMP	Conc	% of Mock		% of Mock
  ID NO 1	ID NO	μM	UBE3A-SUP	sd	UBE3A	sd

  5224	169_2	7.5 μM	49	4	209	9
  5224	169_3	7.5 μM	47	5	282	5
  5224	169_4	7.5 μM	57	14	202	12
  5224	169_5	7.5 μM	84	36	148	4
  5224	169_6	7.5 μM	42	1	285	16
  5224	169_7	7.5 μM	52	6	233	27
  5224	169_8	7.5 μM	51	7	278	11
  5224	169_9	7.5 μM	51	4	228	20
  5224	169_10	7.5 μM	78	17	143	5
  5224	169_11	7.5 μM	74	15	146	2
  5224	169_12	7.5 μM	47	1	277	26
  5224	169_13	7.5 μM	56	23	244	42
  5224	169_14	7.5 μM	74	16	141	1
  5224	169_15	7.5 μM	95	32	122	13
  5224	169_16	7.5 μM	44	4	276	23
  5224	169_17	7.5 μM	85	5	118	5
  5224	169_18	7.5 μM	75	18	131	4
  5224	169_19	7.5 μM	95	18	126	11
  5224	169_20	7.5 μM	61	12	169	20
  5224	169_21	7.5 μM	79	18	156	3
  5224	169_22	7.5 μM	63	14	173	16
  5224	169_23	7.5 μM	43	2	233	27
  5224	169_24	7.5 μM	56	1	183	9
  5224	169_25	7.5 μM	48	0	220	24
  5224	169_26	7.5 μM	41	1	244	39
  5224	169_27	7.5 μM	55	16	260	42
  5224	169_28	7.5 μM	48	1	265	65
  5224	169_29	7.5 μM	56	2	197	18
  5224	169_30	7.5 μM	57	12	189	12
  5224	169_31	7.5 μM	53	4	196	9
  5224	169_32	7.5 μM	50	1	220	3
  5224	169_33	7.5 μM	64	19	227	8
  5224	169_34	7.5 μM	58	4	193	10
  5224	169_35	7.5 μM	45	2	229	3
  5224	169_36	7.5 μM	44	6	262	14
  5224	169_37	7.5 μM	55	2	180	21
  5224	169_38	7.5 μM	75	22	158	13
  5224	169_39	7.5 μM	76	15	159	17
  5224	169_40	7.5 μM	60	18	232	31
  5224	169_41	7.5 μM	46	3	230	10
  5224	169_42	7.5 μM	47	3	240	11
  5224	169_43	7.5 μM	48	9	273	30
  5224	169_44	7.5 μM	83	32	196	11
  5224	169_45	7.5 μM	69	4	185	20
  5224	169_46	7.5 μM	45	9	256	3
  5224	169_47	7.5 μM	41	2	304	4
  5224	169_48	7.5 μM	44	1	260	16
  5224	169_49	7.5 μM	38	1	245	32
  5224	169_50	7.5 μM	35	2	314	28
  5224	169_51	7.5 μM	41	5	281	5
  5224	169_52	7.5 μM	36	1	282	1
  5224	169_53	7.5 μM	38	7	301	7
  5224	169_54	7.5 μM	36	3	304	6
  5224	169_55	7.5 μM	52	5	246	23
  5224	169_56	7.5 μM	33	15	302	15
  5224	169_57	7.5 μM	34	16	273	16
  5784	570_1	7.5 μM	47	0	274	7
  5784	570_2	7.5 μM	47	8	232	8
  5784	570_3	7.5 μM	55	25	280	54
  5784	570_4	7.5 μM	61	11	235	54
  5784	570_5	7.5 μM	72	10	198	30
  5784	570_6	7.5 μM	66	8	244	50
  5784	570_7	7.5 μM	42	1	284	13
  5784	570_8	7.5 μM	43	6	257	11
  5784	570_9	7.5 μM	32	9	242	30
  5785	571_1	7.5 μM	40	1	269	35
  5785	571_2	7.5 μM	42	3	187	6
  5785	571_3	7.5 μM	46	6	242	8
  5785	571_4	7.5 μM	37	4	282	19
  5785	571_5	7.5 μM	48	16	296	2
  5785	571_6	7.5 μM	37	6	274	10
  5785	571_7	7.5 μM	39	1	260	8
  5785	571_8	7.5 μM	35	1	252	3
  5785	571_9	7.5 μM	30	5	297	10
  5786	572_1	7.5 μM	34	4	279	29
  5786	572_2	7.5 μM	63	10	152	4
  5786	572_3	7.5 μM	39	0	280	42
  5786	572_4	7.5 μM	40	1	283	14
  5786	572_5	7.5 μM	38	6	310	11
  5786	572_6	7.5 μM	33	1	316	18
  5786	572_7	7.5 μM	35	1	318	11
  5786	572_8	7.5 μM	47	9	310	19
  5786	572_9	7.5 μM	31	7	321	12
  8116	573_1	7.5 μM	39	8	316	28
  8116	573_2	7.5 μM	49	15	305	41
  8116	573_3	7.5 μM	46	13	308	3
  8116	573_4	7.5 μM	39	3	332	6
  8116	573_5	7.5 μM	34	6	278	12
  8116	573_6	7.5 μM	42	1	285	10
  8116	573_7	7.5 μM	38	0	289	33
  8116	573_8	7.5 μM	40	4	311	20
  8116	573_9	7.5 μM	57	9	315	5
  8117	574_1	7.5 μM	40	2	291	35
  8117	574_2	7.5 μM	42	3	343	18
  8117	574_3	7.5 μM	36	6	325	8
  8117	574_4	7.5 μM	38	1	279	15
  8117	574_5	7.5 μM	42	6	308	10
  8117	574_6	7.5 μM	47	8	340	11
  8117	574_7	7.5 μM	43	0	308	42
  8117	574_8	7.5 μM	44	6	268	10
  8117	574_9	7.5 μM	41	8	241	22
  8118	575_1	7.5 μM	47	0	198	28
  8118	575_2	7.5 μM	83	26	253	31
  8118	575_3	7.5 μM	48	4	348	5
  8118	575_4	7.5 μM	37	2	269	7
  8118	575_5	7.5 μM	43	6	258	17
  8118	575_6	7.5 μM	50	6	286	3
  8118	575_7	7.5 μM	37	2	331	30
  8118	575_8	7.5 μM	47	7	264	1
  8118	575_9	7.5 μM	64	23	243	3
  8119	576_1	7.5 μM	47	1	272	14
  8119	576_2	7.5 μM	109	31	119	3
  8119	576_3	7.5 μM	36	3	287	6
  8119	576_4	7.5 μM	35	3	285	23
  8119	576_5	7.5 μM	49	10	222	1
  8119	576_6	7.5 μM	79	12	132	10
  8119	576_7	7.5 μM	76	4	132	3
  8119	576_8	7.5 μM	62	1	147	5
  8119	576_9	7.5 μM	43	3	230	5
  8120	577_1	7.5 μM	57	3	158	15
  8120	577_2	7.5 μM	39	4	279	60
  8120	577_3	7.5 μM	38	1	290	68
  8120	577_4	7.5 μM	77	11	148	11
  8120	577_5	7.5 μM	31	6	272	36
  8120	577_6	7.5 μM	38	8	228	32
  8120	577_7	7.5 μM	40	8	246	39
  8120	577_8	7.5 μM	43	11	256	26
  8120	577_9	7.5 μM	85	32	109	6
  8584	578_1	7.5 μM	57	7	199	7
  8584	578_2	7.5 μM	40	5	263	3
  8584	578_3	7.5 μM	40	2	289	23
  8584	578_4	7.5 μM	43	8	199	16
  8584	578_5	7.5 μM	42	1	256	15
  8584	578_6	7.5 μM	42	6	241	10
  8584	578_7	7.5 μM	42	5	329	20
  8584	578_8	7.5 μM	49	7	271	13
  8584	578_9	7.5 μM	45	3	222	3
  8585	579_1	7.5 μM	45	0	208	8
  8585	579_2	7.5 μM	51	4	226	6
  8585	579_3	7.5 μM	54	5	178	8
  8585	579_4	7.5 μM	41	4	328	13
  8585	579_5	7.5 μM	50	5	272	3
  8585	579_6	7.5 μM	86	12	161	0
  8585	579_7	7.5 μM	72	5	155	15
  8585	579_8	7.5 μM	57	3	230	14
  8585	579_9	7.5 μM	83	0	123	1
  8586	580_1	7.5 μM	37	2	313	13
  8586	580_2	7.5 μM	43	1	266	3
  8586	580_3	7.5 μM	42	5	303	5
  8586	580_4	7.5 μM	57	4	225	26
  8586	580_5	7.5 μM	51	4	228	35
  8586	580_6	7.5 μM	44	4	253	15
  8586	580_7	7.5 μM	50	1	241	10
  8586	580_8	7.5 μM	44	0	227	26
  8586	580_9	7.5 μM	31	5	323	31
  8587	581_1	7.5 μM	50	6	223	30
  8587	581_2	7.5 μM	66	7	199	19
  8587	581_3	7.5 μM	56	8	197	9
  8587	581_4	7.5 μM	57	12	270	24
  8587	581_5	7.5 μM	51	12	259	12
  8587	581_6	7.5 μM	39	4	282	2
  8587	581_7	7.5 μM	38	11	263	5
  8587	581_8	7.5 μM	45	10	203	19
  8587	581_9	7.5 μM	43	2	234	10
  9209	582_1	7.5 μM	61	7	225	7
  9209	582_2	7.5 μM	46	9	341	36
  9209	582_3	7.5 μM	44	9	306	38
  9209	582_4	7.5 μM	43	1	249	5
  9209	582_5	7.5 μM	33	16	306	6
  9209	582_6	7.5 μM	37	8	329	19
  9209	582_7	7.5 μM	44	9	289	4
  9209	582_8	7.5 μM	39	3	314	20
  9209	582_9	7.5 μM	41	4	299	25
  9210	583_1	7.5 μM	43	5	319	25
  9210	583_2	7.5 μM	53	9	352	5
  9210	583_3	7.5 μM	42	2	362	42
  9210	583_4	7.5 μM	46	5	225	13
  9210	583_5	7.5 μM	39	6	343	21
  9210	583_6	7.5 μM	44	9	298	8
  9210	583_7	7.5 μM	37	5	332	9
  9210	583_8	7.5 μM	42	6	343	25
  9210	583_9	7.5 μM	36	2	341	9
  9211	584_1	7.5 μM	45	5	343	39
  9211	584_2	7.5 μM	42	2	298	22
  9211	584_3	7.5 μM	44	10	321	2
  9211	584_4	7.5 μM	50	1	299	5
  9211	584_5	7.5 μM	44	1	319	25
  9211	584_6	7.5 μM	50	6	323	13
  9211	584_7	7.5 μM	42	4	316	27
  9211	584_8	7.5 μM	53	3	217	11
  9212	208_2	7.5 μM	44	7	312	26
  9212	208_3	7.5 μM	38	2	331	21
  9212	208_4	7.5 μM	47	3	353	11
  9212	208_5	7.5 μM	54	11	348	14
  9212	208_6	7.5 μM	51	12	310	8
  9212	208_7	7.5 μM	60	9	224	11
  9213	209_2	7.5 μM	44	12	242	21
  9213	209_3	7.5 μM	37	12	335	12
  9213	209_4	7.5 μM	55	7	350	2
  9213	209_5	7.5 μM	47	7	337	19
  9213	209_6	7.5 μM	51	8	300	19
  9213	209_7	7.5 μM	47	15	342	23
  9213	209_8	7.5 μM	45	12	289	5
  9213	209_9	7.5 μM	41	1	368	37
  9213	209_10	7.5 μM	40	4	315	1
  11511	585_1	7.5 μM	41	7	350	12
  11511	585_2	7.5 μM	44	4	233	7
  11511	585_3	7.5 μM	40	8	310	31
  11511	585_4	7.5 μM	33	8	324	41
  11511	585_5	7.5 μM	29	3	314	23
  11511	585_6	7.5 μM	38	4	332	15
  11511	585_7	7.5 μM	30	2	315	15
  11511	585_8	7.5 μM	36	11	328	37
  11511	585_9	7.5 μM	39	5	303	49
  11512	586_1	7.5 μM	60	3	236	5
  11512	586_2	7.5 μM	40	9	282	53
  11512	586_3	7.5 μM	36	1	279	11
  11512	586_4	7.5 μM	34	3	288	21
  11512	586_5	7.5 μM	30	1	270	4
  11512	586_6	7.5 μM	29	5	269	24
  11512	586_7	7.5 μM	33	4	263	6
  11512	586_8	7.5 μM	32	4	270	4
  11512	586_9	7.5 μM	33	5	310	48
  11513	587_1	7.5 μM	45	2	237	34
  11513	587_2	7.5 μM	44	3	307	4
  11513	587_3	7.5 μM	37	1	285	24
  11513	587_4	7.5 μM	44	1	252	41
  11513	587_5	7.5 μM	51	7	220	29
  11513	587_6	7.5 μM	41	2	262	35
  11513	587_7	7.5 μM	39	7	280	21
  11513	587_8	7.5 μM	48	9	230	11
  11513	587_9	7.5 μM	41	5	270	9
  11514	588_1	7.5 μM	54	9	204	25
  11514	588_2	7.5 μM	98	5	143	4
  11514	588_3	7.5 μM	55	9	180	1
  11514	588_4	7.5 μM	113	24	109	17
  11514	588_5	7.5 μM	66	26	150	5
  11514	588_6	7.5 μM	74	1	131	1
  11514	588_7	7.5 μM	79	4	140	9
  11514	588_8	7.5 μM	49	2	235	2
  11514	588_9	7.5 μM	51	10	281	2
  11515	589_1	7.5 μM	61	2	154	9
  11515	589_2	7.5 μM	70	9	126	12
  11515	589_3	7.5 μM	53	3	212	32
  11515	589_4	7.5 μM	93	14	108	14
  11515	589_5	7.5 μM	69	11	191	7
  11515	589_6	7.5 μM	53	9	183	20
  11515	589_7	7.5 μM	45	8	257	4
  11515	589_8	7.5 μM	35	5	213	5
  11515	589_9	7.5 μM	41	2	290	22
  13223	236_2	7.5 μM	39	6	286	21
  13223	236_3	7.5 μM	32	10	256	29
  13223	236_4	7.5 μM	37	5	285	12
  13223	236_5	7.5 μM	33	8	280	19
  13223	236_6	7.5 μM	40	16	295	7
  13223	236_7	7.5 μM	45	10	254	50
  13223	236_8	7.5 μM	41	22	306	50
  13223	236_9	7.5 μM	32	11	292	47
  13223	236_10	7.5 μM	31	10	307	3
  13223	236_11	7.5 μM	52	32	198	29
  13223	236_12	7.5 μM	31	7	261	18
  13223	236_13	7.5 μM	34	3	279	32
  13223	236_14	7.5 μM	38	0	285	75
  13223	236_15	7.5 μM	40	17	307	53
  13223	236_16	7.5 μM	41	6	321	30
  13224	237_2	7.5 μM	49	18	251	38
  13224	237_3	7.5 μM	53	14	236	33
  13224	237_4	7.5 μM	39	0	283	26
  13224	237_5	7.5 μM	43	2	243	2
  13224	237_6	7.5 μM	39	10	265	48
  13224	237_7	7.5 μM	50	3	302	19
  13224	237_8	7.5 μM	46	7	327	43
  13224	237_9	7.5 μM	38	9	287	12
  13224	237_10	7.5 μM	35	6	248	35
  13224	237_11	7.5 μM	41	1	259	24
  13224	237_12	7.5 μM	33	6	303	35
  13224	237_13	7.5 μM	26	4	265	53
  13224	237_14	7.5 μM	30	8	321	15
  13224	237_15	7.5 μM	33	11	315	24
  13224	237_16	7.5 μM	36	11	292	19
  13225	239_2	7.5 μM	35	16	291	30
  13225	239_3	7.5 μM	40	15	311	42
  13225	239_4	7.5 μM	81	6	144	16
  13225	239_5	7.5 μM	90	16	127	11
  13225	239_6	7.5 μM	49	29	282	3
  13225	239_7	7.5 μM	35	4	296	23
  13225	239_8	7.5 μM	40	1	292	48
  13225	239_9	7.5 μM	36	1	318	44
  13225	239_10	7.5 μM	49	NA	304	NA
  13225	239_11	7.5 μM	45	NA	258	NA
  13225	239_12	7.5 μM	43	1	285	1
  13225	239_13	7.5 μM	31	1	308	31
  13225	239_14	7.5 μM	41	8	253	6
  13225	239_15	7.5 μM	28	3	291	16
  13225	239_16	7.5 μM	29	3	314	14
  13226	590_1	7.5 μM	34	1	283	18
  13226	590_2	7.5 μM	49	7	213	17
  13226	590_3	7.5 μM	40	1	274	51
  13226	590_4	7.5 μM	36	1	300	2
  13226	590_5	7.5 μM	37	3	280	36
  13226	590_6	7.5 μM	38	2	204	17
  13226	590_7	7.5 μM	38	5	245	16
  13226	590_8	7.5 μM	30	6	219	34
  13226	590_9	7.5 μM	33	1	269	2
  13226	590_10	7.5 μM	33	2	258	49
  13226	590_11	7.5 μM	48	17	297	31
  13226	590_12	7.5 μM	33	4	317	65
  13226	590_13	7.5 μM	35	7	337	43
  13226	590_14	7.5 μM	25	1	306	22
  13226	590_15	7.5 μM	30	5	299	2
  15113	591_1	7.5 μM	43	3	313	14
  15113	591_2	7.5 μM	52	2	295	24
  15114	592_1	7.5 μM	53	2	232	17
  15114	592_2	7.5 μM	39	1	309	23
  15114	592_3	7.5 μM	46	1	278	12
  15114	592_4	7.5 μM	36	1	328	13
  15114	592_5	7.5 μM	49	9	295	40
  15114	592_6	7.5 μM	46	3	297	10
  15114	592_7	7.5 μM	75	21	160	23
  15114	592_8	7.5 μM	41	10	325	23
  15114	592_9	7.5 μM	55	15	265	3
  15115	241_2	7.5 μM	66	18	168	2
  15115	241_3	7.5 μM	51	15	265	11
  15115	241_4	7.5 μM	49	4	239	7
  15115	241_5	7.5 μM	52	11	314	20
  15115	241_6	7.5 μM	41	13	307	7
  15115	241_7	7.5 μM	38	6	344	33
  15115	241_8	7.5 μM	39	10	329	9
  15115	241_9	7.5 μM	50	11	321	32
  15115	241_10	7.5 μM	48	9	316	1
  15563	593_1	7.5 μM	38	10	282	14
  15563	593_2	7.5 μM	31	5	279	16
  15563	593_3	7.5 μM	34	7	281	16
  15563	593_4	7.5 μM	32	16	318	2
  15563	594_1	7.5 μM	40	2	320	21
  15563	594_2	7.5 μM	54	7	237	14
  15563	594_3	7.5 μM	35	6	300	45
  15563	594_4	7.5 μM	37	7	254	6
  15564	596_1	7.5 μM	47	7	225	35
  15564	596_2	7.5 μM	49	2	184	14
  15564	596_3	7.5 μM	34	8	271	18
  15564	596_4	7.5 μM	45	8	277	29
  15564	595_1	7.5 μM	42	4	254	6
  15564	595_2	7.5 μM	36	9	277	35
  15564	595_3	7.5 μM	40	8	295	31
  15564	595_4	7.5 μM	45	5	173	20
  15566	597_1	7.5 μM	48	6	296	22
  15566	597_2	7.5 μM	44	12	293	8
  15566	597_3	7.5 μM	41	6	318	23
  15566	597_4	7.5 μM	60	9	340	72
  15567	38_3	7.5 μM	41	3	306	14
  15567	38_4	7.5 μM	45	1	303	48
  15567	38_5	7.5 μM	39	15	292	28
  15567	38_6	7.5 μM	46	12	261	40
  15567	598_1	7.5 μM	42	2	257	31
  15567	598_2	7.5 μM	41	12	272	46
  15567	598_3	7.5 μM	54	9	281	29
  15567	598_4	7.5 μM	45	8	307	6
  15568	599_1	7.5 μM	47	3	326	68
  15568	599_2	7.5 μM	60	14	307	30
  15568	599_3	7.5 μM	50	8	274	24
  15568	599_4	7.5 μM	45	6	250	12
  15568	600_1	7.5 μM	37	6	251	1
  15568	600_2	7.5 μM	45	11	267	15
  15568	600_3	7.5 μM	44	5	278	1
  15568	600_4	7.5 μM	41	10	265	5
  15569	601_1	7.5 μM	42	12	271	18
  15569	601_2	7.5 μM	38	6	269	24
  15569	601_3	7.5 μM	39	4	260	34
  15569	601_4	7.5 μM	56	8	146	1
  15570	244_2	7.5 μM	46	1	338	6
  15570	244_3	7.5 μM	47	0	275	47
  15570	244_4	7.5 μM	47	8	281	67
  15570	244_5	7.5 μM	41	8	258	52
  15570	39_2	7.5 μM	53	4	339	25
  15570	39_3	7.5 μM	65	5	200	17
  15570	39_4	7.5 μM	47	7	321	6
  15570	39_5	7.5 μM	46	3	289	20
  15571	602_1	7.5 μM	34	5	278	29
  15571	602_2	7.5 μM	39	8	254	37
  15571	602_3	7.5 μM	41	10	266	23
  15571	602_4	7.5 μM	42	8	256	40
  15571	40_2	7.5 μM	58	0	325	4
  15571	40_3	7.5 μM	58	2	326	35
  15571	40_4	7.5 μM	54	1	306	3
  15571	40_5	7.5 μM	44	2	322	4
  15571	40_6	7.5 μM	43	4	293	17
  15571	40_7	7.5 μM	53	7	343	20
  15571	40_8	7.5 μM	52	1	337	17
  15572	604_1	7.5 μM	58	1	289	3
  15572	604_2	7.5 μM	63	12	230	5
  15572	604_3	7.5 μM	57	3	306	23
  15572	604_4	7.5 μM	46	6	324	4
  15572	603_1	7.5 μM	60	7	339	31
  15572	603_2	7.5 μM	70	0	279	19
  15572	603_3	7.5 μM	59	9	290	48
  15572	603_4	7.5 μM	85	11	123	24
  15573	605_1	7.5 μM	56	5	288	3
  15573	605_2	7.5 μM	58	4	286	6
  15573	605_3	7.5 μM	59	3	261	9
  15573	605_4	7.5 μM	69	24	328	17
  15573	606_1	7.5 μM	50	4	282	19
  15573	606_2	7.5 μM	112	NA	133	NA
  15573	606_3	7.5 μM	55	22	254	43
  15573	606_4	7.5 μM	107	59	116	2
  15574	607_1	7.5 μM	56	2	337	31
  15574	607_2	7.5 μM	59	1	254	10
  15574	607_3	7.5 μM	53	0	295	26
  15574	607_4	7.5 μM	48	3	268	15
  25248	608_1	7.5 μM	86	7	189	5
  25248	608_2	7.5 μM	102	13	136	3
  25248	608_3	7.5 μM	54	17	280	12
  25248	608_4	7.5 μM	71	8	219	31
  25248	608_5	7.5 μM	59	20	179	16
  25248	608_6	7.5 μM	71	2	198	0
  25248	608_7	7.5 μM	47	3	230	21
  25248	608_8	7.5 μM	55	12	287	13
  25248	608_9	7.5 μM	66	19	297	18
  25249	609_1	7.5 μM	58	19	264	7
  25249	609_2	7.5 μM	88	6	156	5
  25249	609_3	7.5 μM	76	19	140	13
  25249	609_4	7.5 μM	50	15	185	6
  25249	609_5	7.5 μM	95	29	139	1
  25249	609_6	7.5 μM	86	15	126	7
  25249	609_7	7.5 μM	72	9	174	1
  25249	609_8	7.5 μM	64	3	189	18
  25249	609_9	7.5 μM	77	12	223	35
  25250	610_1	7.5 μM	55	17	233	7
  25250	610_2	7.5 μM	52	15	233	9
  25250	610_3	7.5 μM	77	5	151	11
  25250	610_4	7.5 μM	48	0	242	21
  25250	610_5	7.5 μM	59	8	234	0
  25250	610_6	7.5 μM	59	12	208	23
  25250	610_7	7.5 μM	69	7	216	5
  25250	610_8	7.5 μM	70	16	211	2
  25250	610_9	7.5 μM	77	22	157	19
  25251	611_1	7.5 μM	43	4	306	10
  25251	611_2	7.5 μM	43	1	300	36
  25251	611_3	7.5 μM	43	17	306	6
  25251	611_4	7.5 μM	40	1	320	37
  25251	611_5	7.5 μM	48	9	273	7
  25251	611_6	7.5 μM	51	2	302	26
  25251	611_7	7.5 μM	40	8	326	8
  25251	611_8	7.5 μM	55	10	330	17
  25251	611_9	7.5 μM	40	3	297	11
  25252	612_1	7.5 μM	58	9	219	5
  25252	612_2	7.5 μM	54	9	282	4
  25252	612_3	7.5 μM	56	13	265	35
  25252	612_4	7.5 μM	81	16	239	51
  25252	612_5	7.5 μM	57	2	234	25
  25252	612_6	7.5 μM	76	18	221	8
  25252	612_7	7.5 μM	45	7	285	11
  25252	612_8	7.5 μM	50	8	231	4
  25252	612_9	7.5 μM	51	3	305	17
  29636	271_1	7.5 μM	35	4	345	29
  29636	271_1	7.5 μM	32	6	383	31
  29636	271_1	7.5 μM	42	7	292	13
  29636	271_1	7.5 μM	40	1	309	41
  29636	271_1	7.5 μM	41	10	339	17
  29636	271_1	7.5 μM	35	8	306	40
  29636	271_1	7.5 μM	33	1	320	12
  29636	271_1	7.5 μM	43	1	347	7
  29636	271_1	7.5 μM	36	2	339	19
  29636	271_1	7.5 μM	36	1	315	5
  29636	271_1	7.5 μM	41	1	326	16
  29636	271_1	7.5 μM	38	2	344	1
  29636	271_1	7.5 μM	34	6	341	8
  29636	271_1	7.5 μM	42	9	320	1
  29636	271_1	7.5 μM	31	8	344	37
  29636	271_1	7.5 μM	44	2	335	11
  29636	271_1	7.5 μM	32	0	316	17
  29636	271_1	7.5 μM	43	11	323	2
  29636	271_1	7.5 μM	35	7	340	2
  29636	271_1	7.5 μM	43	1	340	8
  29636	271_1	7.5 μM	33	4	296	27
  29636	271_1	7.5 μM	38	5	334	4
  29636	271_1	7.5 μM	36	4	341	22
  29636	271_1	7.5 μM	48	4	334	3
  29636	271_1	7.5 μM	36	8	303	13
  29636	271_1	7.5 μM	36	0	343	7
  29636	271_1	7.5 μM	39	1	326	1
  29636	271_1	7.5 μM	38	2	346	14
  29636	271_1	7.5 μM	32	0	332	11
  29636	271_1	7.5 μM	39	4	330	23
  29636	271_1	7.5 μM	39	7	346	33
  29636	271_1	7.5 μM	40	1	329	14
  29636	271_1	7.5 μM	34	6	316	38
  29636	271_1	7.5 μM	33	4	317	14
  29636	271_1	7.5 μM	41	6	328	11
  29636	271_1	7.5 μM	45	2	345	3
  29636	271_1	7.5 μM	37	1	330	3
  29636	271_1	7.5 μM	45	7	322	18
  29636	271_1	7.5 μM	36	3	334	13
  29636	271_1	7.5 μM	33	8	333	3
  29636	271_1	7.5 μM	35	10	321	43
  29636	271_1	7.5 μM	41	3	323	18
  29636	271_1	7.5 μM	39	8	354	39
  29636	271_1	7.5 μM	35	2	327	23
  30599	613_1	7.5 μM	73	29	172	22
  30599	613_2	7.5 μM	87	40	114	9
  30599	613_3	7.5 μM	59	23	168	23
  30599	613_4	7.5 μM	43	15	281	31
  30599	613_5	7.5 μM	51	3	271	28
  30600	614_1	7.5 μM	56	11	179	22
  30600	614_2	7.5 μM	96	40	100	7
  30600	614_3	7.5 μM	41	7	246	27
  30600	614_4	7.5 μM	47	19	283	14
  30600	614_5	7.5 μM	52	21	209	16
  30600	615_1	7.5 μM	61	19	197	12
  30600	615_2	7.5 μM	45	11	287	25
  30600	615_3	7.5 μM	102	NA	115	NA
  30600	615_4	7.5 μM	72	NA	170	NA
  30600	615_5	7.5 μM	95	NA	138	NA
  30601	285_2	7.5 μM	83	NA	165	NA
  30601	285_3	7.5 μM	124	NA	111	NA
  30601	285_4	7.5 μM	69	NA	183	NA
  30601	285_5	7.5 μM	47	23	211	7
  30601	285_6	7.5 μM	46	12	183	6
  30601	617_1	7.5 μM	67	26	190	19
  30601	617_2	7.5 μM	74	35	137	6
  30601	617_3	7.5 μM	51	16	211	4
  30601	617_4	7.5 μM	65	22	142	11
  30601	617_5	7.5 μM	43	8	298	26
  30601	616_1	7.5 μM	50	22	181	12
  30601	616_2	7.5 μM	37	13	276	33
  30601	616_3	7.5 μM	38	16	264	9
  30601	616_4	7.5 μM	43	NA	304	NA
  30601	616_5	7.5 μM	50	NA	229	NA
  30602	619_1	7.5 μM	90	43	131	22
  30602	619_2	7.5 μM	78	40	138	2
  30602	619_3	7.5 μM	66	22	123	8
  30602	619_4	7.5 μM	100	43	96	5
  30602	619_5	7.5 μM	75	17	157	5
  30602	618_1	7.5 μM	46	16	226	12
  30602	618_2	7.5 μM	68	NA	151	NA
  30602	618_3	7.5 μM	52	4	207	18
  30602	618_4	7.5 μM	57	12	223	2
  30602	618_5	7.5 μM	54	2	211	3
  30603	620_1	7.5 μM	106	23	110	16
  30603	620_2	7.5 μM	48	10	243	18
  30603	620_3	7.5 μM	53	1	174	32
  30603	620_4	7.5 μM	81	0	138	15
  30603	620_5	7.5 μM	56	5	218	9
  30604	621_1	7.5 μM	39	4	304	10
  30604	621_2	7.5 μM	35	7	311	3
  30604	621_3	7.5 μM	67	18	142	8
  30604	621_4	7.5 μM	34	6	273	21
  30604	621_5	7.5 μM	36	5	266	18
  30605	622_1	7.5 μM	42	1	242	28
  30605	622_2	7.5 μM	31	10	300	8
  30605	622_3	7.5 μM	35	3	319	11
  30605	622_4	7.5 μM	37	4	281	5
  30605	622_5	7.5 μM	39	5	306	11
  30606	623_1	7.5 μM	47	3	287	1
  30606	623_2	7.5 μM	74	23	166	7
  30606	623_3	7.5 μM	82	1	149	8
  30606	623_4	7.5 μM	66	9	135	8
  30606	623_5	7.5 μM	78	7	128	12
  30608	624_1	7.5 μM	84	13	185	25
  30608	624_2	7.5 μM	35	2	245	9
  30608	624_3	7.5 μM	31	3	267	9
  30608	624_4	7.5 μM	39	16	257	13
  30608	624_5	7.5 μM	34	3	283	4
  30666	625_1	7.5 μM	45	5	286	39
  30666	625_2	7.5 μM	39	3	280	13
  30666	625_3	7.5 μM	40	10	258	9
  30666	625_4	7.5 μM	41	14	234	39
  30666	625_5	7.5 μM	42	5	293	26
  30666	625_6	7.5 μM	44	0	284	25
  30666	625_7	7.5 μM	46	3	271	4
  30666	625_8	7.5 μM	47	5	256	17
  30666	625_9	7.5 μM	40	7	302	2
  30667	626_1	7.5 μM	38	1	279	10
  30667	626_2	7.5 μM	39	21	329	22
  30667	626_3	7.5 μM	59	12	265	65
  30667	626_4	7.5 μM	39	5	318	25
  30667	626_5	7.5 μM	36	2	302	33
  30667	626_6	7.5 μM	36	6	273	34
  30667	626_7	7.5 μM	30	0	299	29
  30667	626_8	7.5 μM	35	4	277	43
  30667	626_9	7.5 μM	32	3	275	22
  30668	627_1	7.5 μM	71	3	131	11
  30668	627_2	7.5 μM	49	4	226	30
  30668	627_3	7.5 μM	64	5	147	8
  30668	627_4	7.5 μM	52	6	176	9
  30668	627_5	7.5 μM	78	14	108	3
  30668	627_6	7.5 μM	40	1	183	23
  30668	627_7	7.5 μM	85	8	116	2
  30668	627_8	7.5 μM	45	1	128	7
  30668	627_9	7.5 μM	42	5	215	36
  30669	628_1	7.5 μM	90	11	120	15
  30669	628_2	7.5 μM	73	12	124	4
  30669	628_3	7.5 μM	88	2	115	4
  30669	628_4	7.5 μM	54	4	190	18
  30669	628_5	7.5 μM	64	1	138	3
  30669	628_6	7.5 μM	62	4	138	11
  30669	628_7	7.5 μM	55	1	138	13
  30669	628_8	7.5 μM	62	1	140	5
  30669	628_9	7.5 μM	79	10	134	22
  30711	629_1	7.5 μM	42	1	252	47
  30711	629_2	7.5 μM	40	2	295	30
  30711	629_3	7.5 μM	46	1	302	78
  30711	629_4	7.5 μM	41	3	260	16
  30711	629_5	7.5 μM	41	1	284	3
  30711	629_6	7.5 μM	43	0	262	1
  30711	629_7	7.5 μM	43	3	278	65
  30711	629_8	7.5 μM	53	5	234	24
  30711	629_9	7.5 μM	37	4	289	1
  30711	629_10	7.5 μM	47	6	292	6
  30711	629_11	7.5 μM	50	5	224	20
  30712	630_1	7.5 μM	44	2	282	22
  30712	630_2	7.5 μM	45	6	297	23
  30712	630_3	7.5 μM	46	2	272	10
  30713	631_1	7.5 μM	45	2	294	10
  30713	631_2	7.5 μM	42	0	285	14
  30713	631_3	7.5 μM	38	3	319	21
  30713	631_4	7.5 μM	43	3	282	4
  30713	631_5	7.5 μM	54	2	173	17
  30713	631_6	7.5 μM	37	0	315	10
  30713	631_7	7.5 μM	40	4	317	2
  30713	631_8	7.5 μM	44	1	275	5
  30713	631_9	7.5 μM	47	2	233	8
  30713	631_10	7.5 μM	108	18	101	3
  30714	632_1	7.5 μM	48	4	210	4
  30714	632_2	7.5 μM	53	5	256	5
  30714	632_3	7.5 μM	60	5	224	19
  30714	632_4	7.5 μM	89	12	117	11
  30714	632_5	7.5 μM	39	6	312	6
  30714	632_6	7.5 μM	40	2	278	31
  30714	632_7	7.5 μM	86	1	160	21
  30714	632_8	7.5 μM	57	17	278	40
  30714	632_9	7.5 μM	51	7	236	13
  30715	304_2	7.5 μM	53	5	206	18
  30715	304_3	7.5 μM	70	11	142	24
  30715	304_4	7.5 μM	88	1	120	10
  30715	304_5	7.5 μM	82	15	123	7
  30715	304_6	7.5 μM	43	4	264	12
  30715	304_7	7.5 μM	41	5	266	49
  30715	304_8	7.5 μM	43	1	291	12
  30715	304_9	7.5 μM	36	3	285	18
  30715	304_10	7.5 μM	42	1	280	40
  33376	633_1	7.5 μM	53	1	234	50
  33376	633_2	7.5 μM	45	5	301	7
  33376	633_3	7.5 μM	53	7	263	17
  33376	633_4	7.5 μM	53	4	229	22
  33376	633_5	7.5 μM	43	3	264	36
  33376	633_6	7.5 μM	53	5	247	12
  33376	633_7	7.5 μM	49	6	289	6
  33376	633_8	7.5 μM	64	11	238	24
  33376	633_9	7.5 μM	63	2	249	28
  33377	634_1	7.5 μM	57	9	250	14
  33377	634_2	7.5 μM	53	10	265	3
  33377	634_3	7.5 μM	48	2	275	10
  33377	634_4	7.5 μM	39	6	287	12
  33377	634_5	7.5 μM	49	1	255	22
  33377	634_6	7.5 μM	51	2	291	15
  33377	634_7	7.5 μM	47	5	297	16
  33377	634_8	7.5 μM	42	9	311	14
  33377	634_9	7.5 μM	47	5	271	23
  33378	635_1	7.5 μM	56	11	257	3
  33378	635_2	7.5 μM	56	5	213	23
  33378	635_3	7.5 μM	61	8	215	8
  33378	635_4	7.5 μM	58	15	232	16
  33378	635_5	7.5 μM	48	3	316	20
  33378	635_6	7.5 μM	59	5	262	30
  33378	635_7	7.5 μM	55	7	287	15
  33378	635_8	7.5 μM	42	1	284	3
  33378	635_9	7.5 μM	40	0	277	23
  33379	636_1	7.5 μM	50	2	239	7
  33379	636_2	7.5 μM	74	16	204	10
  33379	636_3	7.5 μM	55	4	201	3
  33379	636_4	7.5 μM	54	2	238	7
  33379	636_5	7.5 μM	52	5	207	43
  33379	636_6	7.5 μM	47	3	249	6
  33379	636_7	7.5 μM	48	5	241	1
  33379	636_8	7.5 μM	37	7	304	12
  33379	636_9	7.5 μM	62	9	245	5
  33380	637_1	7.5 μM	39	1	219	25
  33380	637_2	7.5 μM	59	1	197	11
  33380	637_3	7.5 μM	56	1	250	19
  33380	637_4	7.5 μM	53	7	244	36
  33380	637_5	7.5 μM	73	13	297	34
  33380	637_6	7.5 μM	65	1	124	17
  33380	637_7	7.5 μM	74	5	133	5
  33380	637_8	7.5 μM	53	2	207	7
  33380	637_9	7.5 μM	54	15	226	26
  39806	638_1	7.5 μM	37	7	283	31
  39806	638_2	7.5 μM	49	11	291	30
  39806	638_3	7.5 μM	41	1	270	20
  39806	638_4	7.5 μM	42	13	267	9
  39806	638_5	7.5 μM	50	1	184	5
  39806	638_6	7.5 μM	38	1	276	15
  39806	638_7	7.5 μM	56	1	292	4
  39806	638_8	7.5 μM	41	4	267	11
  39806	638_9	7.5 μM	41	4	218	33
  39807	639_1	7.5 μM	48	15	293	30
  39807	639_2	7.5 μM	38	3	269	2
  39807	639_3	7.5 μM	72	5	167	3
  39807	639_4	7.5 μM	69	38	242	36
  39807	639_5	7.5 μM	47	6	303	36
  39807	639_6	7.5 μM	53	6	179	5
  39807	639_7	7.5 μM	51	3	189	8
  39807	639_8	7.5 μM	42	3	185	19
  39807	639_9	7.5 μM	45	3	202	15
  39808	640_1	7.5 μM	39	5	265	7
  39808	640_2	7.5 μM	37	4	272	56
  39808	640_3	7.5 μM	38	3	260	17
  39808	640_4	7.5 μM	33	4	255	2
  39808	640_5	7.5 μM	38	3	253	3
  39808	640_6	7.5 μM	40	8	216	10
  39808	640_7	7.5 μM	39	8	310	7
  39808	640_8	7.5 μM	41	6	282	21
  39808	640_9	7.5 μM	40	5	269	12
  44439	641_1	7.5 μM	35	6	336	32
  44439	641_2	7.5 μM	67	20	161	6
  44439	641_3	7.5 μM	34	9	317	30
  44439	641_4	7.5 μM	62	18	193	9
  44439	641_5	7.5 μM	34	4	280	3
  44439	641_6	7.5 μM	43	1	315	45
  44439	641_7	7.5 μM	45	17	307	53
  44439	641_8	7.5 μM	41	0	294	41
  44439	641_9	7.5 μM	37	2	334	43
  44440	361_2	7.5 μM	36	1	303	15
  44440	361_3	7.5 μM	32	3	315	12
  44440	361_4	7.5 μM	41	1	299	7
  44440	361_5	7.5 μM	40	5	295	6
  44440	361_6	7.5 μM	40	2	296	30
  44440	361_7	7.5 μM	39	1	300	55
  44440	361_8	7.5 μM	45	6	285	45
  44440	361_9	7.5 μM	44	6	321	26
  44440	361_10	7.5 μM	46	7	290	18
  44441	362_2	7.5 μM	50	4	277	4
  44441	362_3	7.5 μM	40	6	296	8
  44441	362_4	7.5 μM	37	5	340	18
  44441	362_5	7.5 μM	45	2	266	21
  44441	362_6	7.5 μM	39	7	263	0
  44441	362_7	7.5 μM	41	12	262	36
  44441	362_8	7.5 μM	35	13	313	6
  44441	362_9	7.5 μM	36	8	300	20
  44441	362_10	7.5 μM	48	10	293	1
  46391	642_1	7.5 μM	51	25	278	6
  46391	642_2	7.5 μM	46	2	303	4
  46391	642_3	7.5 μM	48	3	297	11
  46391	642_4	7.5 μM	45	11	320	37
  46391	642_5	7.5 μM	71	32	303	40
  46391	642_6	7.5 μM	47	15	298	16
  46391	642_7	7.5 μM	38	6	277	5
  46391	642_8	7.5 μM	38	3	280	20
  46391	642_9	7.5 μM	51	20	285	16
  46391	642_10	7.5 μM	32	7	293	20
  46391	642_11	7.5 μM	42	2	291	2
  46391	642_12	7.5 μM	40	3	317	19
  46391	642_13	7.5 μM	39	11	295	5
  46391	642_14	7.5 μM	52	20	295	16
  46391	642_15	7.5 μM	39	8	316	38
  46391	642_16	7.5 μM	35	2	294	30
  46391	642_17	7.5 μM	51	5	292	8
  46391	643_1	7.5 μM	39	4	276	16
  46392	644_1	7.5 μM	39	0	321	7
  46392	644_2	7.5 μM	46	4	308	4
  46392	644_3	7.5 μM	44	1	317	3
  46392	644_4	7.5 μM	38	6	315	11
  46392	645_1	7.5 μM	46	5	342	42
  46392	645_2	7.5 μM	37	5	292	25
  46392	645_3	7.5 μM	46	16	317	30
  46392	645_4	7.5 μM	47	8	381	102
  46392	645_5	7.5 μM	42	2	269	4
  46393	646_1	7.5 μM	49	4	295	2
  46393	646_2	7.5 μM	49	9	304	38
  46393	646_3	7.5 μM	44	6	298	50
  46393	646_4	7.5 μM	43	1	296	41
  46393	646_5	7.5 μM	35	1	260	3
  46393	646_6	7.5 μM	40	2	281	67
  46393	646_7	7.5 μM	38	1	278	44
  46393	646_8	7.5 μM	42	6	262	49
  46393	646_9	7.5 μM	38	3	289	24
  46393	646_10	7.5 μM	38	1	317	4
  46393	646_11	7.5 μM	42	1	320	34
  46393	646_12	7.5 μM	36	5	323	8
  46393	646_13	7.5 μM	41	3	262	27
  46393	646_14	7.5 μM	46	13	315	18
  46393	646_15	7.5 μM	42	4	340	27
  46393	646_16	7.5 μM	45	8	360	14
  46393	646_17	7.5 μM	44	1	303	3
  46393	646_18	7.5 μM	50	2	304	28
  46393	646_19	7.5 μM	54	10	217	25
  51241	425_2	7.5 μM	49	12	296	3
  51241	425_3	7.5 μM	48	6	297	10
  51241	425_4	7.5 μM	52	5	275	25
  51241	425_5	7.5 μM	40	6	284	29
  51241	425_6	7.5 μM	39	5	301	22
  51241	425_7	7.5 μM	39	4	263	13
  51241	425_8	7.5 μM	32	5	188	13
  51241	425_9	7.5 μM	42	5	286	2
  51241	425_10	7.5 μM	34	3	165	17

Example 6—Activity of Exon-Exon Spanning Oligonucleotides
• Oligonucleotides designed to be complementary across exon-exon junctions of SNHG14-023 (ENST00000554726) were tested for their ability to reduce the SNHG14 transcript in the region downstream of SNORD109B (also termed UBE3A suppressor or UBE3A-SUP in the data table). Furthermore, the ability to induce UBE3A mRNA re-expression was analyzed. The oligonucleotides primarily span exon2 and exon3 (i.e. are complementary to a region in exon2 and a region in exon 3).
• The oligonucleotides were screened according to the protocol for screening oligonucleotides in human neuronal cell cultures described in the section Example 5.
• The results are shown in table 9.

• TABLE 9
  Oligonucleotide activity in patient derived human neuronal cell cultures.

  CMP ID	Conc	% of Mock		% of Mock
  NO	μM	UBE3A-SUP	sd	UBE3A	sd

  674_1	7.5 μM	47	2	214	12
  675_1	7.5 μM	44	6	265	10
  676_1	7.5 μM	44	3	284	16
  677_1	7.5 μM	55	19	351	18
  678_1	7.5 μM	41	11	257	1
  656_1	7.5 μM	46	3	140	19
  657_1	7.5 μM	35	7	218	27
  658_1	7.5 μM	38	12	253	43
  659_1	7.5 μM	39	7	274	6
  660_1	7.5 μM	38	8	275	29
  661_1	7.5 μM	43	13	246	21
  662_1	7.5 μM	27	10	290	5
  663_1	7.5 μM	28	0	287	23
  664_1	7.5 μM	27	2	288	14
  665_1	7.5 μM	37	9	321	47
  666_1	7.5 μM	54	1	259	10
  667_1	7.5 μM	47	8	236	2
  647_1	7.5 μM	19	3	300	25
  648_1	7.5 μM	22	7	320	3
  649_1	7.5 μM	34	8	326	2
  650_1	7.5 μM	44	4	292	7
  651_1	7.5 μM	36	5	254	9
  652_1	7.5 μM	21	2	314	18
  653_1	7.5 μM	24	5	299	41
  654_1	7.5 μM	31	2	344	41
  655_1	7.5 μM	60	9	301	3
  668_1	7.5 μM	21	3	297	11
  669_1	7.5 μM	24	5	296	27
  670_1	7.5 μM	30	3	274	55
  671_1	7.5 μM	27	6	263	35
  672_1	7.5 μM	27	6	280	50
  673_1	7.5 μM	33	2	290	19

Example 7—Testing In Vitro Efficacy and Potency of Selected Oligonucleotides
• Based on the screenings in examples 2 to 5 above 52 oligonucleotides were selected for potency and efficacy testing.
• The oligonucleotides were screened in human AS patient derived cells as described in the Materials and Method section “Screening oligonucleotides in human neuronal cell cultures—96 well system” with the following modifications:
• For UBE3a-Sense primer commercially available primers and probe from ThermoFisher: Hs00166580_m1 amplifying a 94 bp sequence in position 838 of refseq ID NM_000462.3 were used.
• Each plate include PBS controls (instead on a non-targeting oligonucleotide) and the positive control oligonucleotides CMP ID NO: 186_1 and 39_1 identified in previous screens were included. The additional control oligonucleotides described in the materials and method section were not included. Oligonucleotide test concentrations were from 31.6 μM to 1 nM using a 10 point half-log dilution. All oligonucleotides were tested in 5 independent experiments in 5 different weeks. In the data QC process some plates were removed from the analysis if these were obvious outliers e.g. no PCR product detected. After this filtration there is a minimum of three independent experiments behind each the reported values.
• The EC50 (UBE3A mRNA re-expression) and IC50 (reduction of the SNHG14 transcript in the region downstream of SNORD109B, also termed UBE3A suppressor or UBE3A-SUP in the data table) were determined after curve fitting using a 4 parameter sigmoidal dose-response model. Fitting was executed using the fit engine available inside the Biobook software by IDBS (XLfit). From the curve-fitting the maximum obtainable up-regulation of UBE3A (UBE3A Max Up) and the maximum obtainable knockdown of UBE3A-SUP (UBE3A-SUP max Kd) were determined. Both are shown as % of control (PBS treated cells). The results are shown in table 10, values are reported as geometric means of each biological replicate.

• TABLE 10
  Oligonucleotide EC50 and IC 50 values and maximum
  UBE3A upregulation and UBE3A suppressor knock down.

  CMP	EC50		IC50		UBE3A		UBE3A-SUP
  ID NO	↑ UBE3A	Sd	↓ UBE3A-SUP	Sd	Max Kd	Sd	max Kd	Sd

  586_9	0.02	0.02	0.01	0.00	329.4	25.5	33.5	3.8
  585_1	0.03	0.01	0.03	0.02	301.6	18.3	31.0	5.3
  572_7	0.03	0.00	0.01	0.03	294.1	30.4	31.3	3.5
  591_1	0.03	0.02	0.01	0.00	387.3	46.0	41.4	2.8
  585_8	0.04	0.02	0.02	0.01	312.3	23.1	35.2	3.3
  626_7	0.04	0.02	0.02	0.00	362.5	44.6	38.7	3.3
  621_2	0.04	0.03	0.02	0.01	264.5	19.6	24.7	3.9
  624_3	0.04	0.03	0.04	0.03	288.1	19.2	29.7	5.2
  169_52	0.04	0.04	0.02	0.01	303.4	23.1	27.3	1.8
  624_5	0.04	0.07	0.01	0.01	249.2	16.3	16.4	1.4
  586_5	0.04	0.01	0.01	0.00	364.4	43.9	30.4	3.3
  626_8	0.04	0.03	0.01	0.01	338.7	24.0	39.1	2.6
  169_50	0.05	0.02	0.02	0.02	280.3	23.0	28.3	2.4
  572_6	0.05	0.01	0.01	0.02	298.5	22.4	36.3	4.0
  639_5	0.05	0.03	0.01	0.00	327.7	22.0	38.2	3.6
  592_2	0.05	0.03	0.02	0.05	364.9	27.1	36.4	3.6
  586_8	0.05	0.03	0.02	0.01	366.6	35.1	38.0	3.9
  625_6	0.06	0.03	0.01	0.00	335.5	34.7	32.5	1.9
  644_3	0.06	0.04	0.01	0.02	298.5	22.0	25.3	1.6
  586_4	0.06	0.03	0.01	0.01	354.3	31.5	33.0	2.3
  642_12	0.06	0.05	0.02	0.01	289.2	14.8	24.7	3.0
  572_5	0.07	0.09	0.02	0.00	312.7	25.9	31.5	3.0
  592_4	0.07	0.06	0.03	0.01	341.1	31.9	35.7	1.8
  622_3	0.07	0.04	0.02	0.01	300.9	21.0	27.6	3.6
  622_5	0.07	0.01	0.02	0.01	306.2	13.5	24.4	4.0
  616_4	0.07	0.04	0.03	0.02	293.8	17.9	29.1	5.0
  304_6	0.08	0.08	0.02	0.00	318.1	39.2	43.8	3.9
  638_8	0.08	0.01	0.01	0.01	354.8	30.6	42.4	4.1
  622_4	0.08	0.07	0.02	0.01	330.3	24.8	29.5	2.4
  642_13	0.08	0.07	0.04	0.03	268.4	21.0	26.8	2.5
  573_8	0.08	0.01	0.04	0.02	320.1	34.4	34.3	3.4
  241_9	0.09	0.04	0.04	0.03	352.6	26.4	34.1	2.3
  304_10	0.09	0.07	0.03	0.01	289.5	19.9	28.3	2.8
  636_8	0.10	0.08	0.03	0.04	330.8	34.1	53.9	13.4
  598_4	0.11	0.06	0.03	0.04	295.0	15.1	41.3	2.2
  586_6	0.11	0.10	0.02	0.02	316.2	21.2	23.8	3.5
  621_1	0.11	0.21	0.02	0.01	311.9	19.2	27.5	5.2
  331_1	0.12	0.02	0.03	0.02	293.6	49.0	25.1	5.4
  626_9	0.13	0.12	0.02	0.03	302.2	32.6	34.4	2.2
  169_56	0.14	0.18	0.02	0.01	356.5	22.3	26.8	2.2
  631_6	0.14	0.30	0.04	0.00	292.9	25.1	33.5	4.9
  186_1	0.16	0.02	0.04	0.05	371.7	70.1	32.5	5.5
  611_7	0.16	0.15	0.02	0.01	369.2	29.3	37.2	3.9
  165_1	0.17	0.02	0.07	0.12	266.3	NA	26.7	NA
  646_16	0.18	0.15	0.03	0.02	306.0	9.0	30.6	2.9
  640_4	0.20	0.10	0.02	0.01	328.4	31.0	40.4	7.0
  631_1	0.22	0.07	0.07	0.02	324.6	1.6	47.5	8.1
  590_13	0.23	0.59	0.02	0.02	353.4	22.3	31.8	2.2
  172_1	0.24	0.10	0.11	0.14	254.2	NA	34.2	NA
  35_2	0.26	0.02	0.06	0.09	257.9	NA	22.3	NA
  425_5	0.26	0.14	0.08	0.08	317.3	33.9	32.9	2.4
  359_1	0.27	0.03	0.03	0.08	260.5	NA	31.3	NA
  209_1	0.28	0.08	0.03	0.03	339.9	30.6	48.2	11.6
  123_1	0.28	0.13	0.26	0.08	235.9	NA	51.8	NA
  361_1	0.29	0.10	0.06	0.02	331.9	17.2	30.7	6.3
  602_1	0.31	0.33	0.15	0.20	340.3	21.7	42.2	5.0
  NA	0.44	0.12	0.15	0.18	251.3	NA	24.6	NA
  287_1	0.45	0.09	0.04	0.02	318.1	45.2	28.8	9.3
  303_1	0.46	0.05	0.09	0.15	259.9	NA	30.9	NA
  379_1	0.47	0.02	0.08	0.16	247.2	NA	22.5	NA
  405_1	0.48	0.42	0.04	0.01	323.0	56.2	32.5	11.9
  39_1	0.51	0.20	0.06	0.06	341.2	30.3	40.4	4.7
  206_1	0.52	0.07	0.14	0.31	262.9	NA	30.5	NA
  155_1	0.53	0.10	NA	0.53	260.8	NA	26.7	NA
  362_1	0.57	0.25	0.09	0.02	328.1	57.3	27.4	8.6
  178_1	0.58	0.35	0.11	0.04	334.3	50.8	26.6	8.0
  48_1	0.59	0.02	0.07	0.56	262.7	NA	27.2	NA
  200_1	0.62	0.51	0.15	0.06	331.0	54.3	33.1	6.2
  361_5	0.67	0.18	0.07	0.00	307.1	22.9	32.1	4.5
  597_4	0.67	0.51	0.10	0.06	325.3	17.3	35.3	2.7
  85_1	0.68	0.06	0.28	0.41	255.5	NA	35.1	NA
  278_1	0.69	0.67	0.08	0.09	313.8	33.4	27.2	4.6
  271_1	0.69	0.00	0.03	0.65	247.3	NA	24.0	NA
  403_1	0.77	0.57	0.11	0.09	296.4	55.0	28.8	7.0
  204_1	0.78	0.59	0.05	0.05	316.1	35.5	36.3	7.9
  116_1	0.91	0.05	0.09	0.43	240.6	NA	31.6	NA
  124_1	0.92	0.29	0.55	0.94	190.0	NA	43.9	NA
  237_8	0.93	0.66	0.05	0.03	376.2	32.8	33.6	3.7
  378_1	0.95	0.64	0.13	0.09	317.7	30.1	48.5	6.1
  126_2	0.95	0.05	0.12	0.70	219.7	NA	45.0	NA
  373_1	1.03	0.63	0.13	0.08	321.7	38.6	27.5	4.8
  641_5	1.16	1.36	0.07	0.06	335.1	28.9	26.6	5.1
  207_1	1.18	0.58	0.18	0.06	318.5	42.9	44.0	7.2
  19_1	1.50	0.19	0.24	1.07	261.7	NA	28.4	NA
  175_1	1.51	0.42	0.17	0.11	333.5	23.8	29.2	5.2
  304_1	1.55	0.09	0.08	0.11	297.8	26.2	32.5	5.7
  399_1	1.86	2.50	0.44	0.26	340.1	52.2	39.6	4.3
  38_1	2.12	0.10	0.34	0.43	257.3	NA	45.1	NA
  222_1	2.29	0.75	0.28	0.12	298.2	34.9	26.8	5.6
  187_1	2.30	1.39	1.00	0.91	315.3	38.4	28.6	6.2
  272_1	2.32	1.39	0.24	0.16	330.4	41.2	37.1	6.1
  18_1	2.42	0.21	0.24	2.00	271.0	NA	29.3	NA
  118_1	2.78	0.30	0.31	0.07	205.4	NA	40.4	NA
  35_1	2.93	4.94	3.61	1.52	258.4	NA	48.2	NA
  233_1	3.14	1.68	0.35	0.16	330.3	20.1	29.3	5.2
  220_1	3.47	0.99	1.02	0.48	315.5	27.4	29.6	7.6
  33_1	3.97	0.41	1.07	NA	265.7	NA	32.2	NA
  109_1	4.06	1.45	1.33	0.67	231.7	44.7	39.6	3.9
  40_1	4.17	0.05	0.12	3.74	263.6	NA	38.3	NA
  115_1	4.98	0.15	0.25	NA	184.2	NA	47.0	NA
  161_1	6.55	3.20	1.25	1.24	294.0	24.8	32.1	7.4
  105_4	6.61	1.62	1.38	4.20	NA	NA	50.6	NA
  19_2	6.66	1.17	3.17	1.52	201.7	NA	57.7	NA
  104_1	7.75	6.77	1.67	1.05	267.9	25.5	42.5	4.1
  18_2	20.00	1.67	3.50	NA	245.9	NA	46.4	NA
  108_1	20.00	0.61	1.27	NA	219.6	NA	51.2	NA
  129_2	20.00	0.08	1.10	NA	165.8	NA	56.5	NA
  141_1	20.00	0.03	0.15	NA	159.0	NA	64.1	NA
  142_1	20.00	1.04	1.12	NA	133.1	NA	57.6	NA
  145_1	20.00	1.30	1.81	NA	139.0	NA	56.9	NA

Claims (24)

1. An antisense oligonucleotide which comprises a contiguous nucleotide sequence of 10 to 30 nucleotides in length with at least 98% complementarity to position 25278410 to 25419462 on human chromosome 15.

2. The oligonucleotide of claim 1, wherein the contiguous nucleotide sequence is complementary to a region of the target nucleic acid of SEQ ID NO: 1 and/or 2.

3. The oligonucleotide of claim 1, wherein the contiguous nucleotide sequence is complementary to a sub-sequence of the target nucleic acid, wherein the sub-sequence is selected from the group consisting of the regions indicated in table 1 or 2.

4. The oligonucleotide of claim 1, wherein the oligonucleotide comprises a sequence selected from the group consisting of SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 1819, 20, 21, 22, 23, 23, 24, 25, 26, 26, 27, 28, 29, 30, 31, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 44, 45, 45, 46, 47, 48, 49, 50, 51, 52, 53, 53, 54, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 79, 80, 81, 8283, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 95, 96, 96, 96, 97, 98, 99, 100, 101, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817 and 818.

5. The oligonucleotide of claim 1, comprising one or more modified nucleosides.

6. The oligonucleotide of claim 5, wherein the one or more modified nucleosides is a 2′ sugar modified nucleoside.

7. The oligonucleotide of claim 6, wherein the one or more 2′ sugar modified nucleoside is independently selected from the group consisting of 2′-O-alkyl-RNA, 2′-O-methyl-RNA, 2′-alkoxy-RNA, 2′-O-methoxyethyl-RNA, 2′-amino-DNA, 2′-fluoro-DNA, arabino nucleic acid (ANA), 2′-fluoro-ANA and LNA nucleosides.

8. The oligonucleotide of claim 5, wherein the one or more modified nucleoside is a LNA nucleoside.

9. The oligonucleotide of claim 1, wherein the oligonucleotide comprises at least one modified internucleoside linkage.

10. The oligonucleotide of claim 9, wherein the internucleoside linkages within the contiguous nucleotide sequence are phosphorothioate internucleoside linkages.

11. The oligonucleotide of claim 1, wherein the oligonucleotide is capable of recruiting RNase H.

12. The oligonucleotide of claim 11, wherein the oligonucleotide is a gapmer.

13. The oligonucleotide of claim 11, wherein the oligonucleotide is a gapmer of formula 5′-F-G-F′-3′, where region F and F′ independently comprise 1-7 modified nucleosides and G is a region between 6 and 16 nucleosides which are capable of recruiting RNaseH.

14. The oligonucleotide of claim 1, wherein the oligonucleotide is selected from the group consisting of CMP ID NO: 4_1, 4_2, 5_1, 5_2, 6_1, 6_2, 7_1, 7_2, 8_1, 9_1, 10_1, 11_1, 11_2, 12_1, 12_2, 13_1, 13_2, 14_1, 15_1, 16_1, 17_1, 17_2, 18_1, 18_2, 19_1, 19_2, 20_1, 21_1, 22_1, 23_1, 23_2, 24_1, 25_1, 26_1, 26_2, 27_1, 28_1, 28_2, 29_1, 29_2, 30_1, 31_1, 31_2, 32_1, 33_1, 34_1, 34_2, 34_3, 34_4, 34_5, 34_6, 34_7, 35_1, 35_2, 36_1, 37_1, 38_1, 38_2, 38_3, 38_4, 38_5, 38_6, 39_1, 39_2, 39_3, 39_4, 39_5, 40_1, 40_2, 40_3, 40_4, 40_, 40_6, 40_7, 40_8, 41_1, 42_1, 43_1, 44_1, 44_2, 45_1, 45_2, 46_1, 47_1, 48_1, 48_2, 48_3, 48_4, 48_5, 48_6, 48_7, 49_1, 50_1, 51_1, 52_1, 53_1, 53_2, 54_1, 54_2, 54_3, 55_1, 55_2, 56_1, 57_1, 58_1, 58_2, 58_3, 59_1, 59_2, 60_1, 60_2, 60_3, 61_1, 62_1, 63_1, 64_1, 64_2, 65_1, 66_1, 67_1, 68_1, 69_1, 69_2, 69_3, 70_1, 70_2, 70_3, 71_1, 72_1, 72_2, 73_1, 73_2, 73_3, 74_1, 74_2, 75_1, 75_2, 76_1, 77_1, 77_2, 77_3, 78_1, 79_1, 79_2, 79_3, 80_1, 80_2, 80_3, 81_1, 82_1, 82_2, 83_1, 83_2, 84_1, 84_2, 85_1, 85_2, 86_1, 87_1, 88_1, 88_2, 89_1, 90_1, 91_1, 92_1, 93_1, 94_1, 95_1, 95_2, 96_1, 96_2, 96_3, 97_1, 97_2, 97_3, 97_4, 98_1, 98_2, 98_3, 99_1, 99_2, 99_3, 99_4, 100_1, 100_2, 100_3, 101_, 101_2, 101_3, 101_4, 102_1, 102_2, 102_3, 102_4, 103_1, 103_2, 103_3, 103_4, 104_1, 104_2, 104_3, 105_1, 105_2, 105_3, 105_4, 106_1, 106_2, 106_3, 106_4, 107_1, 107_2, 107_3, 107_4, 108_1, 108_2, 108_3, 108_4, 109_1, 109_2, 109_3, 109_4, 110_1, 110_2, 111_1, 111_, 111_3, 112_, 112_2, 113_1, 114_1, 115_1, 116_1, 117_1, 118_1, 119_1, 120_1, 120_2, 121_1, 122_1, 123_1, 124_1, 125_1, 126_1, 126_2, 127_1, 128_1, 128_2, 128_3, 128_4, 129_1, 129_2, 130_1, 131_1, 132_1, 132_2, 132_3, 133_1, 133_2, 133_3, 133_4, 134_1, 134_2, 135_1, 135_2, 136_1, 137_1, 138_1, 139_1, 140_1, 141_1, 142_1, 143_1, 144_1, 145_1, 145_2, 146_1, 146_2, 147_1, 148_1, 149_1, 150_1, 150_2, 151_1, 152_1, 153_1, 154_1, 155_1, 156_1, 157_1, 158_1, 159_1, 160_1, 161_1, 162_1, 163_1, 164_1, 165_1, 166_1, 167_1, 168_1, 169_1, 169_10, 169_11, 169_12, 169_13, 169_14, 169_15, 169_16, 169_17, 169_18, 169_19, 169_2, 169_20, 169_21, 169_22, 169_23, 169_24, 169_25, 169_26, 169_27, 169_28, 169_29, 169_3, 169_30, 169_31, 169_32, 169_33, 169_34, 169_35, 169_36, 169_37, 169_38, 169_39, 169_4, 169_40, 169_41, 169_42, 169_43, 169_44, 169_45, 169_46, 169_47, 169_48, 169_49, 169_5, 169_50, 169_51, 169_52, 169_53, 169_54, 169_55, 169_56, 169_57, 169_6, 169_7, 169_8, 169_9, 169_58, 169_59, 169_60, 169_61, 169_62, 170_1, 171_1, 172_1, 173_1, 174_1, 175_1, 176_1, 177_1, 178_1, 179_1, 180_1, 181_1, 182_1, 183_1, 184_1, 185_1, 186_1, 187_1, 188_1, 189_1, 190_1, 191_1, 192_1, 193_1, 194_1, 195_1, 196_1, 197_1, 198_1, 199_1, 200_1, 201_1, 202_1, 203_1, 204_1, 205_1, 206_1, 207_1, 208_1, 208_2, 208_3, 208_4, 208_5, 208_6, 208_7, 209_1, 209_10, 209_2, 209_3, 209_4, 209_5, 209_6, 209_7, 209_8, 209_9, 210_1, 211_1, 212_1, 213_1, 214_1, 215_1, 216_1, 217_1, 218_1, 219_1, 220_1, 221_1, 222_1, 223_1, 224_1, 225_1, 226_1, 227_1, 228_1, 229_1, 230_1, 231_1, 232_1, 233_1, 234_1, 235_1, 236_1, 236_10, 236_11, 236_12, 236_13, 236_14, 236_15, 236_16, 236_2, 236_3, 236_4, 236_5, 236_6, 236_7, 236_8, 236_9, 236_17, 236_18, 236_19, 236_20, 236_21, 237_1, 237_10, 237_11, 237_12, 237_13, 237_14, 237_15, 237_16, 237_2, 237_3, 237_4, 237_5, 237_6, 237_7, 237_8, 237_9, 237_17, 237_18, 237_19, 237_20, 237_21, 238_1, 239_1, 239_10, 239_11, 239_12, 239_13, 239_14, 239_15, 239_16, 239_2, 239_3, 239_4, 239_5, 239_6, 239_7, 239_8, 239_9, 239_17, 239_18, 239_19, 239_20, 239_21, 240_1, 241_1, 241_10, 241_2, 241_3, 241_4, 241_5, 241_6, 241_7, 241_8, 241_9, 241_11, 241_12, 241_13, 241_14, 241_15, 242_1, 243_1, 244_1, 244_2, 244_3, 244_4, 244_5, 245_1, 246_1, 247_1, 248_1, 249_1, 250_1, 251_1, 252_1, 253_1, 254_1, 255_1, 256_1, 257_1, 258_1, 259_1, 260_1, 261_1, 262_1, 263_1, 264_1, 265_1, 266_1, 267_1, 268_1, 269_1, 270_1, 271_1, 272_1, 273_1, 274_1, 275_1, 276_1, 277_1, 278_1, 279_1, 280_1, 281_1, 282_1, 283_1, 284_1, 285_1, 285_2, 285_3, 285_4, 285_5, 285_6, 285_7, 285_8, 285_9, 285_10, 285_11, 286_1, 287_1, 288_1, 289_1, 290_1, 291_1, 292_1, 293_1, 294_1, 295_1, 296_1, 297_1, 298_1, 299_1, 300_1, 301_1, 302_1, 303_1, 304_1, 304_10, 304_2, 304_3, 304_4, 304_5, 304_6, 304_7, 304_8, 304_9, 304_11, 304_12, 304_13, 304_14, 304_15, 305_1, 306_1, 307_1, 308_1, 309_1, 310_1, 311_1, 312_1, 313_1, 314_1, 315_1, 316_1, 317_1, 318_1, 319_1, 320_1, 321_1, 322_1, 323_1, 324_1, 325_1, 326_1, 327_1, 328_1, 329_1, 330_1, 331_1, 332_1, 333_1, 334_1, 335_1, 336_1, 337_1, 338_1, 339_1, 340_1, 341_1, 342_1, 343_1, 344_1, 345_1, 346_1, 347_1, 348_1, 349_1, 350_1, 351_1, 352_1, 353_1, 354_1, 355_1, 356_1, 357_1, 358_1, 359_1, 360_1, 361_1, 361_10, 361_2, 361_3, 361_4, 361_5, 361_6, 361_7, 361_8, 361_9, 362_1, 362_10, 362_2, 362_3, 362_4, 362_5, 362_6, 362_7, 362_8, 362_9, 363_1, 364_1, 365_1, 366_1, 367_1, 368_1, 369_1, 370_1, 371_1, 372_1, 373_1, 374_1, 375_1, 376_1, 377_1, 378_1, 379_1, 380_1, 381_1, 382_1, 383_1, 384_1, 385_1, 386_1, 387_1, 388_1, 389_1, 390_1, 391_1, 392_1, 393_1, 394_1, 395_1, 396_1, 397_1, 398_1, 399_1, 400_1, 401_1, 402_1, 403_1, 404_1, 405_1, 406_1, 407_1, 408_1, 409_1, 410_1, 411_1, 412_1, 413_1, 414_1, 415_1, 416_1, 417_1, 418_1, 419_1, 420_1, 421_1, 422_1, 423_1, 424_1, 425_1, 425_10, 425_2, 425_3, 425_4, 425_5, 425_6, 425_7, 425_8, 425_9, 426_1, 427_1, 428_1, 429_1, 430_1, 431_1, 432_1, 433_1, 434_1, 435_1, 436_1, 437_1, 438_1, 439_1, 440_1, 441_1, 442_1, 443_1, 444_1, 445_1, 446_1, 447_1, 448_1, 449_1, 450_1, 451_1, 452_1, 453_1, 454_1, 455_1, 456_1, 457_1, 458_1, 459_1, 460_1, 461_1, 462_1, 463_1, 464_1, 465_1, 466_1, 467_1, 468_1, 469_1, 470_1, 471_1, 472_1, 473_1, 474_1, 475_1, 476_1, 477_1, 478_1, 479_1, 480_1, 481_1, 482_1, 483_1, 484_1, 485_1, 486_1, 487_1, 488_1, 489_1, 490_1, 491_1, 492_1, 493_1, 494_1, 495_1, 496_1, 497_1, 498_1, 499_1, 500_1, 501_1, 502_1, 503_1, 504_1, 505_1, 506_1, 507_1, 508_1, 509_1, 510_1, 511_1, 512_1, 513_1, 514_1, 515_1, 516_1, 517_1, 518_1, 519_1, 520_1, 521_1, 522_1, 523_1, 524_1, 525_1, 526_1, 527_1, 528_1, 529_1, 530_1, 531_1, 532_1, 533_1, 534_1, 535_1, 536_1, 537_1, 538_1, 539_1, 540_1, 541_1, 542_1, 543_1, 544_1, 545_1, 546_1, 547_1, 548_1, 549_1, 550_1, 551_1, 552_1, 553_1, 554_1, 555_1, 556_1, 557_1, 558_1, 559_1, 560_1, 561_1, 562_1, 563_1, 564_1, 565_1, 566_1, 567_1, 568_1, 569_1, 570_1, 570_2, 570_3, 570_4, 570_5, 570_6, 570_7, 570_8, 570_9, 570_10, 570_11, 570_12, 570_13, 570_14, 571_1, 571_2, 571_3, 571_4, 571_5, 571_6, 571_7, 571_8, 571_9, 571_10, 571_11, 571_12, 571_13, 571_14, 572_1, 572_2, 572_3, 572_4, 572_5, 572_6, 572_7, 572_8, 572_9, 572_10, 572_11, 572_12, 572_13, 572_14, 573_1, 573_2, 573_3, 573_4, 573_5, 573_6, 573_7, 573_8, 573_9, 573_10, 573_11, 573_12, 573_13, 573_14, 574_1, 574_2, 574_3, 574_4, 574_5, 574_6, 574_7, 574_8, 574_9, 574_10, 574_11, 574_12, 574_13, 574_14, 575_1, 575_2, 575_3, 575_4, 575_5, 575_6, 575_7, 575_8, 575_9, 575_10, 575_11, 575_12, 575_13, 575_14, 576_1, 576_2, 576_3, 576_4, 576_5, 576_6, 576_7, 576_8, 576_9, 576_10, 576_11, 576_12, 576_13, 576_14, 577_1, 577_2, 577_3, 577_4, 577_5, 577_6, 577_7, 577_8, 577_9, 577_10, 577_11, 577_12, 577_13, 577_14, 578_1, 578_2, 578_3, 578_4, 578_5, 578_6, 578_7, 578_8, 578_9, 579_1, 579_2, 579_3, 579_4, 579_5, 579_6, 579_7, 579_8, 579_9, 580_1, 580_2, 580_3, 580_4, 580_5, 580_6, 580_7, 580_8, 580_9, 581_1, 581_2, 581_3, 581_4, 581_5, 581_6, 581_7, 581_8, 581_9, 582_1, 582_2, 582_3, 582_4, 582_5, 582_6, 582_7, 582_8, 582_9, 583_1, 583_2, 583_3, 583_4, 583_5, 583_6, 583_7, 583_8, 583_9, 584_1, 584_2, 584_3, 584_4, 584_5, 584_6, 584_7, 584_8, 585_1, 585_2, 585_3, 585_4, 585_5, 585_6, 585_7, 585_8, 585_9, 585_10, 585_11, 585_12, 585_13, 585_14, 586_1, 586_2, 586_3, 586_4, 586_5, 586_6, 586_7, 586_8, 586_9, 586_10, 586_11, 586_12, 586_13, 586_14, 587_1, 587_2, 587_3, 587_4, 587_5, 587_6, 587_7, 587_8, 587_9, 587_10, 587_11, 587_12, 587_13, 587_14, 588_1, 588_2, 588_3, 588_4, 588_5, 588_6, 588_7, 588_8, 588_9, 588_10, 588_11, 588_12, 588_13, 588_14, 589_1, 589_2, 589_3, 589_4, 589_5, 589_6, 589_7, 589_8, 589_9, 589_10, 589_11, 589_12, 589_13, 589_14, 590_1, 590_10, 590_11, 590_12, 590_13, 590_14, 590_15, 590_2, 590_3, 590_4, 590_5, 590_6, 590_7, 590_8, 590_9, 590_16, 590_17, 590_18, 590_19, 590_20, 591_1, 591_2, 592_1, 592_2, 592_3, 592_4, 592_5, 592_6, 592_7, 592_8, 592_9, 592_10, 592_11, 592_12, 592_13, 592_14, 593_1, 593_2, 593_3, 593_4, 594_1, 594_2, 594_3, 594_4, 595_1, 595_2, 595_3, 595_4, 596_1, 596_2, 596_3, 596_4, 597_1, 597_2, 597_3, 597_4, 598_1, 598_2, 598_3, 598_4, 599_1, 599_2, 599_3, 599_4, 600_1, 600_2, 600_3, 600_4, 601_1, 601_2, 601_3, 601_4, 602_1, 602_2, 602_3, 602_4, 603_1, 603_2, 603_3, 603_4, 604_1, 604_2, 604_3, 604_4, 605_1, 605_2, 605_3, 605_4, 606_1, 606_2, 606_3, 606_4, 607_1, 607_2, 607_3, 607_4, 608_1, 608_2, 608_3, 608_4, 608_5, 608_6, 608_7, 608_8, 608_9, 609_1, 609_2, 609_3, 609_4, 609_5, 609_6, 609_7, 609_8, 609_9, 610_1, 610_2, 610_3, 610_4, 610_5, 610_6, 610_7, 610_8, 610_9, 611_1, 611_2, 611_3, 611_4, 611_5, 611_6, 611_7, 611_8, 611_9, 612_1, 612_2, 612_3, 612_4, 612_5, 612_6, 612_7, 612_8, 612_9, 613_1, 613_2, 613_3, 613_4, 613_5, 613_6, 613_7, 613_8, 613_9, 613_10, 614_1, 614_2, 614_3, 614_4, 614_5, 614_6, 614_7, 614_8, 614_9, 614_10, 615_1, 615_2, 615_3, 615_4, 615_5, 615_6, 615_7, 615_8, 615_9, 615_10, 616_1, 616_2, 616_3, 616_4, 616_5, 616_6, 616_7, 616_8, 616_9, 616_10, 617_1, 617_2, 617_3, 617_4, 617_5, 617_6, 617_7, 617_8, 617_9, 617_10, 618_1, 618_2, 618_3, 618_4, 618_5, 618_6, 618_7, 618_8, 618_9, 618_10, 619_1, 619_2, 619_3, 619_4, 619_5, 619_6, 619_7, 619_8, 619_9, 619_10, 620_1, 620_2, 620_3, 620_4, 620_5, 620_6, 620_7, 620_8, 620_9, 620_10, 621_1, 621_2, 621_3, 621_4, 621_5, 621_6, 621_7, 621_8, 621_9, 621_10, 621_11, 622_1, 622_2, 622_3, 622_4, 622_5, 622_6, 622_7, 622_8, 622_9, 622_10, 623_1, 623_2, 623_3, 623_4, 623_5, 623_6, 623_7, 623_8, 623_9, 623_10, 624_1, 624_2, 624_3, 624_4, 624_5, 624_6, 624_7, 624_8, 624_9, 624_10, 625_1, 625_2, 625_3, 625_4, 625_5, 625_6, 625_7, 625_8, 625_9, 625_10, 625_11, 625_12, 625_13, 625_14, 626_1, 626_2, 626_3, 626_4, 626_5, 626_6, 626_7, 626_8, 626_9, 626_10, 626_11, 626_12, 626_13, 626_14, 627_1, 627_2, 627_3, 627_4, 627_5, 627_6, 627_7, 627_8, 627_9, 627_10, 627_11, 627_12, 627_13, 627_14, 628_1, 628_2, 628_3, 628_4, 628_5, 628_6, 628_7, 628_8, 628_9, 628_10, 628_11, 628_12, 628_13, 628_14, 629_1, 629_10, 629_11, 629_2, 629_3, 629_4, 629_5, 629_6, 629_7, 629_8, 629_9, 629_12, 629_13, 629_14, 629_15, 629_16, 630_1, 630_2, 630_3, 631_1, 631_10, 631_2, 631_3, 631_4, 631_5, 631_6, 631_7, 631_8, 631_9, 631_11, 631_12, 631_13, 631_14, 631_15, 632_1, 632_2, 632_3, 632_4, 632_5, 632_6, 632_7, 632_8, 632_9, 632_10, 632_11, 632_12, 632_13, 632_14, 633_1, 633_2, 633_3, 633_4, 633_5, 633_6, 633_7, 633_8, 633_9, 634_1, 634_2, 634_3, 634_4, 634_5, 634_6, 634_7, 634_8, 634_9, 635_1, 635_2, 635_3, 635_4, 635_5, 635_6, 635_7, 635_8, 635_9, 636_1, 636_2, 636_3, 636_4, 636_5, 636_6, 636_7, 636_8, 636_9, 637_1, 637_2, 637_3, 637_4, 637_5, 637_6, 637_7, 637_8, 637_9, 638_1, 638_2, 638_3, 638_4, 638_5, 638_6, 638_7, 638_8, 638_9, 638_10, 638_11, 638_12, 638_13, 638_14, 639_1, 639_2, 639_3, 639_4, 639_5, 639_6, 639_7, 639_8, 639_9, 639_10, 639_11, 639_12, 639_13, 639_14, 640_1, 640_2, 640_3, 640_4, 640_5, 640_6, 640_7, 640_8, 640_9, 640_10, 640_11, 640_12, 640_13, 640_14, 641_1, 641_2, 641_3, 641_4, 641_5, 641_6, 641_7, 641_8, 641_9, 642_1, 642_10, 642_11, 642_12, 642_13, 642_14, 642_15, 642_16, 642_17, 642_2, 642_3, 642_4, 642_5, 642_6, 642_7, 642_8, 642_9, 642_18, 642_19, 642_20, 642_21, 642_22, 643_1, 644_1, 644_2, 644_3, 644_4, 644_5, 644_6, 645_1, 645_2, 645_3, 645_4, 645_5, 645_6, 645_7, 645_8, 645_9, 645_10, 646_1, 646_10, 646_11, 646_12, 646_13, 646_14, 646_15, 646_16, 646_17, 646_18, 646_19, 646_2, 646_3, 646_4, 646_5, 646_6, 646_7, 646_8, 646_9, 646_20, 646_21, 646_22, 646_23, 646_24, 647_1, 648_1, 649_1, 650_1, 651_1, 652_1, 653_1, 654_1, 655_1, 656_1, 657_1, 658_1, 659_1, 660_1, 661_1, 662_1, 663_1, 664_1, 665_1, 666_1, 667_1, 668_1, 669_1, 670_1, 671_1, 672_1, 673_1, 674_1, 675_1, 676_1, 677_1, 678_1, 679_1, 679_2, 679_3, 679_4, 679_5, 680_1, 680_2, 680_3, 680_4, 680_5, 681_1, 681_2, 681_3, 681_4, 681_5, 682_1, 682_2, 682_3, 682_4, 682_5, 683_1, 683_2, 683_3, 683_4, 683_5, 684_1, 684_2, 684_3, 684_4, 684_5, 685_1, 685_2, 685_3, 685_4, 685_5, 686_1, 686_2, 686_3, 686_4, 686_5, 687_1, 687_2, 687_3, 687_4, 687_5, 688_1, 688_2, 688_3, 688_4, 688_5, 689_1, 689_2, 689_3, 689_4, 689_5, 690_1, 690_2, 690_3, 690_4, 690_5, 691_1, 691_2, 692_1, 692_2, 692_3, 692_4, 692_5, 693_1, 693_2, 693_3, 693_4, 693_5, 694_1, 694_2, 694_3, 694_4, 694_5, 695_1, 695_2, 695_3, 695_4, 695_5, 696_1, 696_2, 696_3, 696_4, 696_5, 697_1, 697_2, 697_3, 697_4, 697_5, 698_1, 698_2, 698_3, 698_4, 698_5, 699_1, 699_2, 699_3, 699_4, 699_5, 700_1, 700_2, 700_3, 700_4, 700_5, 701_1, 701_2, 701_3, 701_4, 701_5, 702_1, 702_2, 702_3, 702_4, 702_5, 703_1, 703_2, 703_3, 703_4, 703_5, 704_1, 704_2, 704_3, 704_4, 704_5, 705_1, 705_2, 705_3, 705_4, 705_5, 706_1, 706_2, 706_3, 706_4, 706_5, 707_1, 707_2, 707_3, 707_4, 707_5, 708_1, 708_2, 708_3, 708_4, 708_5, 709_1, 709_2, 709_3, 709_4, 709_5, 710_1, 710_2, 710_3, 710_4, 710_5, 711_1, 711_2, 711_3, 711_4, 711_5, 712_1, 712_2, 712_3, 712_4, 712_5, 713_1, 713_2, 713_3, 713_4, 713_5, 714_1, 714_2, 714_3, 714_4, 714_5, 715_1, 715_2, 715_3, 715_4, 715_5, 716_1, 716_2, 716_3, 716_4, 716_5, 717_1, 717_2, 717_3, 717_4, 717_5, 718_1, 718_2, 719_1, 719_2, 719_3, 719_4, 719_5, 720_1, 720_2, 720_3, 720_4, 720_5, 721_1, 721_2, 721_3, 721_4, 721_5, 722_1, 722_2, 722_3, 722_4, 722_5, 723_1, 723_2, 723_3, 723_4, 723_5, 724_1, 724_2, 724_3, 724_4, 724_5, 725_1, 725_2, 725_3, 725_4, 725_5, 726_1, 726_2, 726_3, 726_4, 726_5, 727_1, 727_2, 727_3, 727_4, 727_5, 728_1, 728_2, 728_3, 728_4, 728_5, 729_1, 729_2, 729_3, 729_4, 729_5, 730_1, 730_2, 730_3, 730_4, 730_5, 731_1, 731_2, 731_3, 731_4, 731_5, 732_1, 732_2, 732_3, 732_4, 732_5, 733_1, 733_2, 733_3, 733_4, 733_5, 734_1, 734_2, 734_3, 734_4, 734_5, 735_1, 735_2, 735_3, 735_4, 735_5, 736_1, 736_2, 736_3, 736_4, 736_5, 737_1, 737_2, 737_3, 737_4, 737_5, 738_1, 738_2, 738_3, 738_4, 738_5, 738_6, 739_1, 739_2, 739_3, 739_4, 739_5, 740_1, 740_2, 740_3, 740_4, 740_5, 741_1, 741_2, 741_3, 741_4, 741_5, 742_1, 742_2, 742_3, 743_1, 743_2, 743_3, 743_4, 743_5, 744_1, 744_2, 744_3, 744_4, 744_5, 745_1, 745_2, 745_3, 745_4, 745_5, 746_1, 746_2, 746_3, 747_1, 747_2, 747_3, 747_4, 747_5, 748_1, 748_2, 748_3, 748_4, 748_5, 749_1, 749_2, 749_3, 749_4, 749_5, 750_1, 750_2, 750_3, 750_4, 751_1, 751_2, 751_3, 751_4, 751_5, 752_1, 752_2, 752_3, 752_4, 752_5, 753_1, 753_2, 753_3, 753_4, 753_5, 754_1, 754_2, 754_3, 754_4, 754_5, 755_1, 755_2, 755_3, 755_4, 755_5, 756_1, 756_2, 756_3, 756_4, 756_5, 757_1, 757_2, 757_3, 757_4, 757_5, 758_1, 758_2, 758_3, 758_4, 758_5, 759_1, 759_2, 759_3, 759_4, 759_5, 760_1, 760_2, 760_3, 760_4, 760_5, 761_1, 761_2, 761_3, 761_4, 761_5, 762_1, 762_2, 762_3, 762_4, 762_5, 763_1, 763_2, 763_3, 763_4, 763_5, 764_1, 764_2, 764_3, 764_4, 764_5, 765_1, 765_2, 765_3, 765_4, 765_5, 766_1, 766_2, 766_3, 766_4, 766_5, 767_1, 767_2, 767_3, 767_4, 767_5, 768_1, 768_2, 768_3, 768_4, 768_5, 769_1, 769_2, 769_3, 769_4, 769_5, 770_1, 770_2, 770_3, 770_4, 770_5, 771_1, 771_2, 771_3, 771_4, 771_5, 772_1, 772_2, 772_3, 772_4, 772_5, 773_1, 773_2, 773_3, 773_4, 773_5, 774_1, 774_2, 774_3, 774_4, 774_5, 775_1, 775_2, 775_3, 775_4, 775_5, 776_1, 776_2, 776_3, 776_4, 776_5, 777_1, 777_2, 777_3, 777_4, 777_5, 778_1, 778_2, 778_3, 778_4, 778_5, 779_1, 779_2, 779_3, 779_4, 779_5, 780_1, 780_2, 780_3, 780_4, 780_5, 781_1, 782_1, 782_2, 782_3, 782_4, 782_5, 783_1, 783_2, 783_3, 783_4, 783_5, 784_1, 784_2, 784_3, 784_4, 784_5, 785_1, 786_1, 786_2, 786_3, 786_4, 786_5, 787_1, 787_2, 787_3, 787_4, 787_5, 788_1, 788_2, 788_3, 788_4, 788_5, 789_1, 789_2, 789_3, 789_4, 789_5, 790_1, 790_2, 790_3, 790_4, 790_5, 791_1, 791_2, 791_3, 791_4, 791_5, 792_1, 792_2, 792_3, 792_4, 792_5, 793_1, 793_2, 793_3, 793_4, 793_5, 794_1, 794_2, 794_3, 794_4, 794_5, 795_1, 795_2, 795_3, 795_4, 795_5, 796_1, 796_2, 796_3, 796_4, 796_5, 797_1, 797_2, 797_3, 797_4, 797_5, 798_1, 798_2, 798_3, 798_4, 798_5, 799_1, 799_2, 799_3, 799_4, 799_5, 800_1, 800_2, 800_3, 800_4, 800_5, 801_1, 801_2, 801_3, 801_4, 801_5, 802_1, 802_2, 802_3, 802_4, 802_5, 803_1, 803_2, 803_3, 803_4, 803_5, 804_1, 804_2, 804_3, 804_4, 804_5, 805_1, 805_2, 805_3, 805_4, 805_5, 806_1, 806_2, 806_3, 806_4, 806_5, 807_1, 807_2, 807_3, 807_4, 807_5, 808_1, 808_2, 808_3, 808_4, 808_5, 809_1, 809_2, 809_3, 809_4, 809_5, 810_1, 810_2, 810_3, 810_4, 810_5, 811_1, 811_2, 811_3, 811_4, 811_5, 812_1, 812_2, 812_3, 812_4, 812_5, 813_1, 813_2, 813_3, 813_4, 813_5, 814_1, 814_2, 814_3, 814_4, 814_5, 815_13, 815_2, 815_3, 815_4, 815_5, 816_1, 816_2, 816_3, 816_4, 816_5, 816_6, 817_1 and 818_1

15. A conjugate comprising the oligonucleotide of claim 1, and at least one conjugate moiety covalently attached to said oligonucleotide.

16. A pharmaceutical composition comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.

17. An in vivo or in vitro method for inducing UBE3A expression in a target cell where expression of paternal UBE3A is suppressed, said method comprising administering an oligonucleotide of claim 1 in an effective amount to said cell.

18. The method according to claim 17, wherein the expression of UBE3A is increased by at least 40% compared to a control.

19. The method according to claim 17, wherein the level of the SNHG14 transcript downstream of SNORD109B is reduced by at least 30% compared to a control.

20. The method according to claim 17, wherein the target cell is a neuronal cell.

21. The method according to claim 17, wherein the expression of SNORD115 is not significantly affected compared to a control.

22. A method for treating or preventing a disease comprising administering a therapeutically or prophylactically effective amount of an oligonucleotide of claim 1 to a subject suffering from or susceptible to Angelman syndrome.

23. The oligonucleotide of claim 1 for use in the treatment or prevention of Angelman syndrome.

24. Use of the oligonucleotide of claim 1 for the preparation of a medicament for treatment or prevention of Angelman syndrome.

Images